Journal of Oncology Pharmacy Practice

Dostarlimab: A promising new PD-1 inhibitor for cancer immunotherapy

Objective Dostarlimab, a humanized monoclonal PD-1 blocking antibody, is being tested as a cancer therapy in this review. Specifically, it addresses mismatch repair failure in endometrial cancer and locally progressed rectal cancer patients. Data Sources A thorough database search found Dostarlimab clinical trials and studies. Published publications and ongoing clinical trials on Dostarlimab's efficacy as a single therapy and in conjunction with other medicines across cancer types were searched. Data Summary The review recommends Dostarlimab for endometrial cancer mismatch repair failure, as supported by GARNET studies. The analysis also highlights locally advanced rectal cancer findings. In the evolving area of cancer therapy, immune checkpoint inhibitors including pembrolizumab, avelumab, atezolizumab, nivolumab, and durvalumab were discussed. Conclusions Locally advanced rectal cancer patients responded 100% to Dostarlimab. Many clinical trials, including ROSCAN, AMBER, IOLite, CITRINO, JASPER, OPAL, PRIME, PERLA, and others, are investigating Dostarlimab in combination treatment. This research sheds light on Dostarlimab's current and future possibilities, in improving cancer immunotherapy understanding.

Cisplatin-induced bone marrow failure in an adult patient with Fanconi anemia

Introduction Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure typically developing in the first decade of life, congenital abnormalities, and an increased predisposition to malignancy. However, patients with FA can remain undiagnosed until adulthood and present with solid organ malignancies. Due to impaired DNA repair mechanisms, patients with FA are highly susceptible to severe bone marrow toxicity when treated with cisplatin. Case Report A 38-year-old woman, diagnosed with locally advanced squamous cell carcinoma (SCC) of the uterine cervix, underwent treatment with weekly cisplatin concurrent with radiotherapy. After the second week of cisplatin treatment, she presented with severe pancytopenia. The prolonged and severe pancytopenia following cisplatin and radiation, along with cervical SCC in the absence of risk factors and the presence of parental consanguinity, raised the possibility of FA as the underlying cause. Whole exome sequencing revealed a homozygous FANCI c.668A > C (p.Lys223Thr) missense variant confirming the diagnosis of FA. Management and Outcome The pancytopenia exhibited a protracted course, necessitating admission and supportive treatment with antibiotics, red blood cell and platelet transfusions, as well as filgrastim and eltrombopag. Eventually, the pancytopenia improved after approximately 40 days of hospitalization. Discussion SCC of the head and neck or gynecologic organs in a young adult without known risk factors should prompt consideration of FA. Cisplatin should be avoided in patients with FA.

Chemotherapy regimen for recurrent uterine leiomyosarcoma

Introduction Uterine leiomyosarcoma is a rare gynecological malignancy, the limited literature indicated that doxorubicin alone or gemcitabine/docetaxel combination is the preferred chemotherapy regimen. Given the rarity of the disease and the lack of high-level clinical evidence, there is no consensus on the best treatment. Case report We report a case of a patient with uterine leiomyosarcoma who recurred after adjustment treatment with doxorubicin, gemcitabine, docetaxel, and anlotinib; and required a new chemotherapy regimen. Management and outcomes The follow-up chemotherapy regimen was doxorubicin-liposome 40 mg/m2 on one day in combination with dacarbazine 250 mg/m2 on one to five days of intravenous infusion every 21 days. We monitored adverse effects during chemotherapy and the process was smooth. Discussion It is important to comprehensively consider the patient's condition, and fully consider the efficacy, dosage, and adverse reactions of the chemotherapy regimen to determine the appropriate plan, in order to achieve the best therapeutic benefits for patients.

Gemcitabine-induced dilated-cardiomyopathy in patient with platinum-refractory ovarian-cancer: A case report and literature review

Introduction Gemcitabine is a nucleoside analog and pyrimidine antimetabolite that inhibits RNA synthesis, currently approved for use to treat a variety of cancers, among which ovarian cancers. Gemcitabine is considered relatively safe and it is generally well tolerated, with rarely reported cardiac side effects. Case report We report a case of gemcitabine induced dilated cardiomyopathy in a 41-year-old woman receiving gemcitabine as second line treatment for platinum-resistant ovarian cancer without pre-existing hypertension or significant cardiac history. Management and Outcome: The patient presented with clinical symptoms and laboratory and imaging results suggestive of congestive cardiac failure, with a left ventricular ejection fraction of 15%. Gemcitabine administration was stopped and Furosemide with ACE-inhibitors and Beta-blocker agents were initiated. At that point the clinical situation improved: symptoms and findings disappeared with gemcitabine cessation. Discussion Our case demonstrated for the first time objective evidence for dilated cardiomyopathy induced by gemcitabine in a young patient with platinum-resistant ovarian cancer without pre-existing significant cardiac history. Although rare, gemcitabine-induced cardiotoxicity should be promptly recognized in order to take appropriate measures to manage it.

Novel approach of desensitization in allergic reaction to Olaparib

Introduction PARP (Poly ADP Ribose Polymerase) inhibitors are an effective maintenance therapy for various entities, such as BRCA (breast cancer gene) mutated or HRD (homologous recombination deficiency) positive primary platin-sensitive advanced ovarian cancer after platin induction therapy and in relapse after responding to carboplatin reinduction. Other entities are metastatic BRCA mutated pancreas, prostate and Her2-negative breast cancer. Therefore, patients with allergic reactions to PARP inhibitors should undergo a desensitization procedure to be able to receive this efficient therapy. Case report We conducted a two-day desensitization on a 45-year-s old patient with advanced ovarian cancer who displayed symptoms of an allergic reaction to Olaparib. Management and outcome Using an Olaparib tablet suspension, we orally administered increasing Olaparib doses, starting with 12.5 mg and reaching a cumulative dose of 387.5 mg on the first day and starting with 100 mg and reaching a cumulative dose of 600 mg on the second day, without concomitant antiallergic medication. Except for mild erythema on day one receding within the hour, no further allergic reactions appeared during desensitization. The patient has since received 300 mg of Olaparib twice a day without further complications or interruptions. Conclusion Desensitization in a two-day suspension protocol is a safe method that ensures effective maintenance therapy for patients with allergic reactions to PARP inhibitors.

Pharmacological profile and potential drug interactions in ovarian cancer hospitalized patients

The aim of this study was to identify the main therapeutic classes prescribed to ovarian cancer patients and the potential drug interactions (PDI) during hospitalization. This descriptive retrospective work was carried out in a referral gynecological cancer hospital from the Brazilian public health system. The first 24 h inpatients’ prescriptions were evaluated to obtain the pharmacological profile data. Clinical and epidemiological characteristics were collected through the analysis of electronic medical records. A total of 236 patients were included in the study, of which 154 (65.25%) had PDI, with a mean of 1.43 ± 1.76 interactions per patient. The main therapeutic classes prescribed were analgesics and antiemetics (35%), compatible with the oncologic supportive care. All PDI identified (n = 331) were categorized by severity, using the Micromedex database, resulting in: 1.51% contraindicated, 67.67% major, 24.77% moderate, and 6.04% minor. The more prevalent PDI were ondansetron/tramadol (22.05%) and metoclopramide/tramadol (7.25%), both major. An association between PDI and polypharmacy was observed, which did not occur between age or length of stay. Ongoing prescription review by the pharmaceutical team is necessary to identify, monitor, and manage PDI-related adverse events and carry out required interventions with patients, physicians, and nurses. Taken together the data showed that even in a specialized hospital, the complexity of the pharmacotherapy can cause harm to the ovarian cancer patient. The clinical pharmacist acting in a multidisciplinary team is important for improving patient safety in oncology services.

Complete metabolic response after carboplatin desensitization in Peritoneal Carcinomatosis

Introduction High-grade serous primary peritoneal cancer is highly sensitive to platinum-based chemotherapy with response rates above 80%. Incidence of immediate hypersensitivity reactions to carboplatin is estimated to be between 15% and 20%, usually seen after a mean of 6–8 infusions, with patients developing moderate to severe reactions. Case report A 62-year-old female patient with stage IIIC primary high-grade serous carcinoma of the peritoneum was diagnosed and chemotherapy with carboplatin and Paclitaxel was indicated by the oncology service and patient shows response. At 6 months the patient returns, a new PET/CT reports progression of the disease. Carboplatin/paclitaxel cycles are restarted and in the eight cycle of carboplatin within 40 min of administration, she presented severe anaphylaxis with skin, pulmonary, cardiac and atypical symptoms. Infusion is suspended and intramuscular epinephrine with hydrocortisone and chlorphenamine are administered resolving symptoms. Management and outcome Intradermal skin test with carboplatin at the concentration of 10 mg / ml (dilution 1: 100) was positive. Due to the symptoms presented and to continue the safe reintroduction to carboplatin, a 4 bag 16-step drug desensitization protocol was carried out at a total dose of 620 mg with no hypersensitivity reactions. Discussion Prolonged carboplatin use is associated with an increased incidence of carboplatin-related hypersensitivity reactions. And in patients that present hypersensitivity reactions, a safe and effective carboplatin desensitization protocol can be carried out to reach the administration of a full dose. Desensitization protocol induces tolerance to a drug temporarily and is dependent on continuous exposure.

Fatal hepatitis B reactivation in a patient receiving chemoradiation for cervical cancer

Introduction Hepatitis B virus (HBV) infection remains a global public health threat, with approximately 257 million people suffering from chronic HBV infection worldwide in 2015. HBV reactivation is a known complication of immunosuppressive therapy in people suffering with chronic HBV. Medications commonly associated with HBV reactivation include B-cell depleting agents and anthracycline derivatives. There have been very few documented cases of chemoradiation inducing HBV reactivation among scientific literature. Case report A 44-year-old woman with chronic HBV infection and [FIGO] stage IIIB cervical cancer developed marked transaminitis and increased HBV viral load after receiving treatment with three doses of cisplatin and one dose of carboplatin with concurrent radiation for cervical cancer. Management and outcome: The patient was admitted for acute liver failure and quickly developed encephalopathy, with treatment complicated by coagulopathy, hypoglycemia, and metabolic acidosis. The patient remained unresponsive to maximal therapeutic efforts and was mechanically ventilated for airway protection. She subsequently died after experiencing ventricular tachycardia followed by asystole. Discussion There are currently no standardized guidelines for the screening of HBV infection or prophylaxis treatment algorithm for patients undergoing chemoradiation. When initiating treatment with immunosuppressive therapy, it is important to screen all patients for chronic HBV infection and to work with an interdisciplinary team of oncologists, hepatologists, and pharmacists to initiate prophylactic antiviral therapy and closely monitor to minimize the risk of HBV reactivation.

Assessment of adverse events among cervical cancer patients at Kenyatta National Hospital

Introduction Due to their cytotoxic nature, anticancer drugs and radiotherapy have the potential to cause toxic adverse events. As a result, they can increase the risk of morbidity and mortality. However, there was a lack of data among cervical cancer patients in our setting. Hence, this study was aimed to assess the prevalence of adverse events among cervical cancer patients at Kenyatta National Hospital. Methods A cross-sectional study design was employed among a consecutive sample of 151 adult cervical cancer patients. The data were collected by reviewing the medical records and interviewing the patients. The data were entered and analyzed using SPSS 27.0 software. The results were presented with frequency tables and graphs. Results A total of 214 adverse events (prevalence of 100%) were identified from 151 patients. The most common adverse events identified were ulcerated sores (52.8%), dysuria (7.5%), thrombocytopenia (5.6%), and loss of appetite (5.6%). The majority of the patients (80.8%) who had adverse events were on radiotherapy. As per the Naranjo causality assessment scale, the predominant (80.1%) proportion of the adverse event was a probable adverse event with a total score of 5–8. Besides, 15.9% of the adverse events had a possible causality. The present study also reported that 61.6% of patients with a probable adverse event were treated with radiotherapy. Conclusion The prevalence of adverse events among cervical patients was high in our setting. The predominant proportion of the adverse event was a probable adverse event and most of them were treated with radiotherapy.

A review of the novel tissue factor antibody–drug conjugate: Tisotumab vedotin

Objective To review and compare the pharmacology, efficacy, and safety of the novel tissue factor antibody–drug conjugate, tisotumab vedotin Data sources Literature search was performed through PubMed MEDLINE, Google Scholar, ClinicalTrials.gov, and the Food and Drug Administration. Data summary Tisotumab vedotin, a novel tissue factor antibody–drug conjugate, was granted accelerated approval by the US FDA on 20 September 2021 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Tisotumab vedotin demonstrated clinical efficacy in a number of solid tumors in innovaTV 201 and more specifically in cervical cancer in the pivotal phase 2 innovaTV 204. In the single-arm innovaTV 204 study, 101 patients with recurrent or metastatic cervical cancer received intravenous tisotumab vedotin at the recommended dose of 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The independent review committee confirmed an objective response rate of 24% with 7% complete responses and 17% partial responses. Tisotumab vedotin is associated with several notable adverse events with data from innovaTV 204 including ocular toxicity, hemorrhage, and peripheral neuropathy. Ninety-two percent of patients experienced treatment-related adverse events with 28% experiencing an adverse event of grade 3 or higher. Conclusions Metastatic cervical cancer has a high risk of relapse with few effective second-line therapeutic options. Current guidelines recommend single agent tisotumab vedotin as a possible option. Ongoing trials will further define its place in therapy.

Assessment of cisplatin-induced nephrotoxicity and its associated factors among cervical cancer patients in the leading tertiary hospital in Kenya

Introduction Cisplatin is the widely used antineoplastic agent in managing cervical cancer despite nephrotoxicity being a major concern. In addition, there was a paucity of data about the degree of nephrotoxicity due to cisplatin in the study setting. Therefore, this study aimed to investigate the prevalence of cisplatin nephrotoxicity among cervical patients. Methods A retrospective cross-sectional study was conducted at the Cancer Treatment Centre of Kenyatta National Hospital among 100 cervical cancer patients treated with a cisplatin regimen. Simple random sampling was employed to the recruit medical record of patients. This study used a data abstraction tool to extract the patients' relevant socio-demographic and clinical characteristics. The data were analysed using Statistical Package for Social Sciences version 25.0 software. Frequency tables and figures were used to present the findings of the study. Binary logistic regression analysis was used to determine factors associated with cisplatin nephrotoxicity. Results The study showed a mean age of 52.09 ± 10.44 years. The prevalence rate of cisplatin-induced nephrotoxicity in cervical cancer patients was 45%. Of these patients, 36% and 9% patients had grade 1 and 2 nephrotoxicities, respectively. Comorbidities (crude odd's ratio (COR) = 3.05, 95% confidence interval [CI] = 1.3–7.02, p = 0.011), hypertension (COR = 3.0, 95% CI = 1.1–7.8, p = 0.03), and more than three cycles of cisplatin treatment (adjusted odd's ratio = 4.5, 95% CI = 1.19–17.0, p = 0.027) were significant factors of nephrotoxicity. Conclusion The prevalence of cisplatin-induced nephrotoxicity among cervical cancer patients was high in the study setting. Comorbidities, number of cycles and types of comorbidities were significant factors associated with cisplatin nephrotoxicity.

Development and reliability testing of a cervical cancer patients knowledge and practice of self-care management of treatment-related adverse events questionnaire

Introduction Cervical cancer (CC) treatment-related adverse events (AEs) were found to be among the major reasons for treatments delays and medication non-adherence. Knowledge and practice of self-care management of these AEs are therefore needed to complement the pharmacotherapeutic interventions. Instruments for assessing CC patients’ knowledge and practice of self-care management of treatment-related Adverse Events (AEs) are lacking. Hence, the rational for this study. Methods A prospective, cross-sectional study was conducted on CC patients receiving chemotherapy, radiotherapy or both, with or without surgery in Usmanu Danfodiyo University Teaching Hospital (UDUTH) Sokoto, a tertiary hospital in North-Western Nigeria. A panel of 14 experts judged the content validity of the items initially selected. Purposive sampling technique was used, 31 CC patients were recruited and interviewed for the questionnaire pre-testing. Descriptive statistics and psychometric analysis were conducted using SPSS Version 20.0 for Windows. A Cronbach’s alpha coefficient ≥0.70 was considered acceptable. Results A 12-domain questionnaire instrument was developed. Eight (57.1%) of the expert panelists rated the questions’ items as “Very good for the study” and none of them rated any of the content “not relevant for the study”. The reliability studies showed that the overall knowledge and practice questions response rates were 71.0% and 77.4% and Cronbach's alpha (α) values were 0.956 and 0.913, respectively. Conclusion A reliable, 12-domain cervical cancer patients’ knowledge and practice of self-care management of treatment-related adverse events questionnaire was developed. Further research on the psychometric qualities of the instrument is needed.

Health-related quality of life among cervical cancer patients at Kenyatta National Hospital

Background Previous study showed that health-related quality of life (HRQoL) was adversely affected during treatment of cervical cancer, with a worsening global score. Therefore, this study aimed to determine the HRQoL of cervical cancer patients at Kenyatta National Hospital. Methods A cross-sectional study design was employed among cervical cancer patients. All eligible consecutive samples of 103 cervical cancer patients were included in the study. Following consent, patients were interviewed using The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire 30 (EORTC QLQ-30) and Cervical Cancer Module CX24 (EORTC QLQ-CX24). The data were entered and analyzed using the SPSS version 20.0 software. Univariate and multivariate binary logistic regression analysis was employed to investigate the predictors of HRQoL. A p-value of ≤ 0.05 was considered statistically significant. Results The majority (69%) of the patients had a poor overall quality of life while 31% of study participants had a good quality of life. Patients with early-stage disease were 7.3 times (AOR = 7.3, 95% CI = 2.4–21.7, p = 0.000) more likely to have a good HRQoL than patients with advanced-stage disease. Patients with no comorbidities were 3.1 times (COR = 3.1, 95% CI = 1.1–9.1, p = 0.037) more likely to have a good HRQoL than patients with comorbidities. Conclusion The overall HRQoL among cervical cancer patients was poor in the setting. Advanced stage of disease and presence of comorbidities were the significant predictors of poor quality of life.

Innovative strategies for cisplatin desensitization in hyperthermic intraperitoneal chemotherapy of ovarian cancer

We present a case of a 41-year-old female diagnosed with Granulosa Cell Tumor (GCT) EC IVB who developed a hypersensitivity reaction (HSR) to carboplatin during the sixth cycle of treatment and subsequently underwent successful intraperitoneal desensitization with cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC). The patient experienced a severe HSR 30 min after carboplatin infusion, presenting with generalized rash, pruritus, nausea, chest pain, and dyspnea. The infusion was halted, and she was treated with intramuscular epinephrine (0.50 mg), intravenous chloropyramine (20 mg), and 250 mL saline, resolving symptoms. Platinum skin tests were subsequently performed and yielded negative results for carboplatin, cisplatin, and oxaliplatin. Following multidisciplinary consensus, cytoreductive surgery with HIPEC and intraperitoneal desensitization to cisplatin was planned. The patient had a peritoneal carcinomatosis index (PCI) of 17. Cytoreductive surgery included omentectomy, appendectomy, resection of mesenteric implants, diaphragmatic and parietal peritonectomy, in bloc hysterectomy, bilateral salpingo-oophorectomy, and pelvic peritonectomy, achieving a completeness of cytoreduction (CC-0). HIPEC was performed with cisplatin (100 mg/m²) at 42°C for 140 min. A desensitization protocol with intraperitoneal cisplatin (180 mg in 8 incremental steps over 140 min) was successfully completed without adverse reactions. Platinum-based chemotherapeutics are frequently associated with HSR, with increasing incidence upon repeated exposure. Intraperitoneal administration, as in HIPEC, may reduce systemic hypersensitivity risks. While prior cases have demonstrated safe HIPEC administration of cisplatin in patients with oxaliplatin-induced HSR, no documented cases exist of intraperitoneal drug desensitization in this context. Our case suggests that intraperitoneal desensitization with cisplatin may be a viable alternative for patients with systemic HSR to platinum agents. Further research is required to establish safety protocols, cross-reactivity risks, and efficacy outcomes for this approach.

Treatment of BRCA 1 mutated breast cancer with a PARP inhibitor and an Immune Checkpoint Inhibitor

Introduction Triple negative breast cancer (TNBC) has traditionally been challenging to treat due to its lack of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2), which were perceived as the only “targets” for treatment of breast cancer. Since 2017, targeted treatment options, such as olaparib, have been approved for the treatment of germline BReast CAncer gene (BRCA) mutated breast cancer, and immune checkpoint inhibitors for TNBC. Case Report A 45-year-old female was diagnosed with BRCA1 mutated TNBC and ovarian cancer in 2018, and adjuvant treatment was partially completed. In 2020, her CA-125 rose and olaparib was initiated. Due to tolerability, she stopped treatment and transitioned to surveillance. In 2021, imaging showed brain metastases, and she started capecitabine. In November 2021 she progressed and transferred care to us. Management and Outcome Due to suspected dual metastatic TNBC and ovarian cancers, and ovarian tissue demonstrating a combined positive score (CPS) of 3, gemcitabine, carboplatin and pembrolizumab were initiated. After six cycles, imaging demonstrated resolution of brain lesions, and pembrolizumab maintenance was continued. In March 2023, she switched to carboplatin, paclitaxel and bevacizumab, due to suspected progression of her ovarian cancer and resolution of breast cancer. She continued until December 2023 and switched to olaparib and bevacizumab. Discussion There is limited data to support sequential use of immunotherapy following treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor. The case report presented here demonstrates successful treatment of a patient with BRCA1 mutated TNBC treated with pembrolizumab after olaparib.

Safety and oncological effectiveness after desensitization in patients with previous hypersensitivity reactions to chemotherapy

Introduction Taxanes and platinum are first-line treatments in gynecological tumors with high rates of hypersensitivity reactions (HSRs), leading to discontinuation of treatment. Desensitization involves induction of temporary tolerance to previously sensitized medications. The aims of this study are to describe HSRs to paclitaxel and carboplatin and evaluate the safety and effectiveness of desensitization protocols in gynecological cancer patients. Methods Original, retrospective, descriptive, analytical study, approved by Bioethics and Research Committee, included >18-year-old patients with gynecological tumors experiencing HSRs to first-line chemotherapy. Patients underwent 3-bag-12-step desensitization. Results 174 desensitization (95 paclitaxel, 79 carboplatin) in 33 female patients, mean age 45.5 years (18–71y). Cancer diagnosis: breast 8 (24.2%), ovarian 14 (42.2%), endometrial 2 (6.1%) and cervix 9 (27.2%). HSR occurred in paclitaxel during cycles 1–2 and in carboplatin after 6 cycles. The most frequently seen HSR symptom was cardiovascular with paclitaxel (94.7%), and cutaneous (93.3%) with carboplatin. Three-bags 12-steps desensitization protocol (initial dilution 1:100) in 5.67hrs. All patients reached total dose desensitization: 82% with no reaction, 12% mild, 6% moderate and 0% severe reaction. Mean disease-free interval and progression-free interval in months (m): breast cancer 29 m and 14 m, ovarian 22 m and 9 m, endometrial 40 m and cervical cancer: 67.5 m and 27 m. Twenty-five patients (73.5%) are still alive. Conclusion HSRs to paclitaxel manifest in the first 1–2 cycles and to carboplatin after 6 cycles. Symptoms include cardiovascular, atypical neuromuscular and urticaria. Changing treatment lines impacts prognosis. Our study revealed that ovarian cancer patients undergoing desensitization protocols achieved longer progression-free intervals. All patients successfully reached total dose desensitization. This study provides evidence of the effectiveness and safety of desensitization and promising perspective for continuing first-line treatment with HSRs.

Efficacy and safety of niraparib in platinum-sensitive recurrent ovarian cancer: retrospective observational study in a tertiary hospital

Background Niraparib has been authorized for maintenance treatment of epithelial ovarian cancer after first-line treatment with platinum, in partial or complete response. Objectives To evaluate the effectiveness and safety of maintenance niraparib in platinum-sensitive recurrent ovarian cancer (PSROC) patients in a tertiary hospital. Materials and Methods This retrospective observational unicentre study included women diagnosed with ovarian adenocarcinoma who received niraparib. Eligibility criteria encompassed women with PSROC, in response to platinum chemotherapy, and not previously treated with other PARPis . Data on demographics, comorbidities, BRCA mutation status, disease stage, treatment history and adverse events were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results A total of 33 patients were included, with a median age of 63.5 years. The majority of patients received niraparib at 200 mg/day based on Research on Adverse Drug Events and Report criteria. Median OS was 30 months (95% CI: 16.76–43.23), and median PFS was 8 months (95% CI: 2.48–13.52). Adverse effects were more frequent during the initial months of treatment, with most classified as CTCAE v5 grade 1–2. Dose reductions, interruption of treatment and discontinuations were observed due to haematologic toxicities primarily. Conclusion This real-world study showed that maintenance niraparib in PSROC patients had effectiveness and safety profiles consistent with clinical trials and other observational studies. Median PFS and OS were comparable to previous reports, and most adverse events were manageable with dose modifications. The results support the use of niraparib as a maintenance therapy option in this patient population.

Evaluation of the management of PARP inhibitor toxicities in ovarian and endometrial cancer within a multi-institution health-system

Introduction Poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) have become a cornerstone of therapy in the management ovarian cancer and other cancers. PARPi are associated with significant toxicities and management strategies are primarily founded on clinical trial experience. This study aimed to provide an evaluation of patients receiving PARPi therapy within an academic health-system. Methods A retrospective, observational study of adult patients with gynecologic malignancy was conducted at the University of Pennsylvania Health System. Data was collected on patients prescribed a PARPi between December 2014 and October 2019. The primary endpoint was the status of PARPi therapy at the end of the study period. Key secondary endpoints included toxicity management strategies, time to discontinuation due to toxicity, progression free survival (PFS), and overall survival (OS). Results Of the 85 patients included, 45 (53%) received olaparib, 24 (28%) niraparib, and 16 (19%) rucaparib. Twenty-nine patients (34%) continued on therapy, 15 (18%) discontinued due to toxicity, and 41 (48%) discontinued due to progression. Fifty-one percent of patients required a dose reduction due to toxicities. The median time to discontinuation due to toxicity was 69 days (9-353). Median PFS was 181 days (9-365) and median OS was 338 days (9-365). Conclusion PARPi therapy is associated with numerous toxicities that are best managed through a multi-modal approach. Importantly, about half the patients in the current study required a dose reduction. Overall, this observational study outlines the incidence of PARPi toxicities and reviews potential management strategies, further guiding practitioners in an area with limited real-world experience.

Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy

Introduction Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. Case report We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome. Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. Discussion As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.

The effect of Bevacizumab treatment on the incidence of hypertension in patients with ovarian cancer: a systematic review and meta-analysis

Introduction This study aims to evaluate the effect of bevacizumab treatment on the incidence of hypertension in patients with ovarian cancer. Methods A comprehensive search of PubMed, Scopus, Embase, Cochrane, Web of Science, and Google Scholar databases was conducted until August 2024. We included only randomized clinical trials that compared ovarian cancer patients treated with Bevacizumab to those treated with other therapies. The primary outcome was the relative risk (RR) of developing hypertension, stratified by grade. Statistical analyses were performed using a random-effects model to account for heterogeneity between studies. Subgroup analyses were conducted based on hypertension severity (grade ≥2 and grade ≥3) and disease stage. Sensitivity analyses and publication bias assessments were also performed. Results A total of 11 randomized trials were included, comprising 5212 patients. The meta-analysis revealed that patients receiving Bevacizumab had a significantly higher risk of hypertension compared to controls (RR = 2.91, 95% CI: 1.65–5.16, P = 0.0002). Subgroup analysis showed that the risk of grade ≥2 hypertension was 1.68 times higher (95% CI: 0.92–3.07), and grade ≥3 hypertension was 5.10 times higher (95% CI: 2.46–10.55) in the Bevacizumab group. Sensitivity analysis confirmed the robustness of these findings, and no significant publication bias was detected. Conclusion Bevacizumab treatment in ovarian cancer significantly increases the risk of hypertension, particularly severe hypertension (grade ≥3). These findings underscore the need for vigilant blood pressure monitoring and management in patients receiving Bevacizumab to mitigate cardiovascular complications and optimize treatment outcomes.

Niraparib-induced pure red cell aplasia

Introduction Niraparib, a strong poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, contributed significantly to progression-free survival as a maintenance therapy in the platinum-sensitive period in both first-line and recurrent ovarian cancer, regardless of the BRCA mutation. Grade 3–4 anemia, which has a manageable side effect profile, especially hematological, is seen in almost 1 out of every 4 patients. To the best of our knowledge, there has been no reported case of pure red cell aplasia (PRCA) induced by niraparib treatment. Case Report A 65-year-old woman diagnosed with stage 3 serous carcinoma of the tuba received niraparib front-line maintenance treatment had grade 4 anemia after 3 months of niraparib treatment. She underwent bone marrow aspiration and biopsy because of refractory anemia, which needs red blood cell (RBC) transfusions despite interruption of treatment. Management and Outcome The patient was treated with 1 mg/kg methyl prednisolone, after histopathological assessment was consistent with PRCA. The hemoglobin count returned to the normal range with steroid treatment. Discussion In daily practice, it should be kept in mind that in the case of refractory anemia induced by niraparib, the underlying cause might be PRCA and can be improved with steroid administration.

A retrospective, real-life analysis of metronomic oral single-agent cyclophosphamide for the treatment of platinum-pretreated advanced ovarian carcinoma in Italy

Introduction Metronomic oral cyclophosphamide (MOC) presents many potential advantages, such as significantly less severe side effects than standard regimens, ease of administration, and the delivery of a dose-dense but not necessarily dose-intense treatment. These observations prompted us to evaluate in a retrospective, multicenter study the efficacy and toxicity of MOC in a real-life series of pretreated cancer patients. Methods The study is a multicenter, retrospective analysis of the activity of single-agent MOC in patients with recurrent or residual epithelial ovarian, fallopian tube, or primary. Eligible patients were continuously treated with MOC at 50 mg/day until progression, toxicity, or death. Overall response rate (ORR), stable disease (SD), and disease control rate (DCR) were reported. Results The study included 62 patients. Three patients reached a complete response rate (5%), 11 had a partial response rate (18), and 15 had stabilization of disease (24) for an ORR of 23% and a DCR of 47%. Patients with low-grade indolent tumors showed an ORR and an SD rate higher than that observed in non-indolent ones (33% vs. 18% and 28% vs. 14%, respectively). Overall, progression-free survival was 3.5 months (range 1–9 months). Conclusion Single-agent MOC is active and very well tolerated in a significant fraction of patients with refractory, recurrent, or residual epithelial ovarian, fallopian tube, or primary peritoneal cancer. In the vision of a practical approach, single-agent MOC may be a useful palliative treatment option for patients with poor tolerance to high-dose regimens or widely pretreated. Further studies are needed better to characterize the role of such an approach in clinical practice.

Medication-related problems among patients with cervical cancers at oncology centers of University of Gondar comprehensive specialized hospital: A hospital-based retrospective study

Introduction Though drugs play indispensable role in the treatment of cervical cancer, they are associated with medication-related problems (MRPs). Hence, the present study was aimed to investigate MRPs among patients with cervical cancer. Methods A hospital-based retrospective study was employed at the oncology center of University of Gondar Comprehensive Specialized Hospital. All patients with cervical cancer diagnosis from January 1, 2016 to December 31, 2020, were included. Stata version 16/MP for Windows was used for description and analysis. Logistic regression analysis was employed. Results A total of 124 patients with cervical cancer were included. Paclitaxel and cisplatin (69.4%) combination were the most widely used treatment regimen. MRPs were found in 59.7% patients, with a mean of 2.22 ± 1.13. Subtherapeutic dose (24.4%), the need for additional drug therapy (22.6%), and adverse drug reactions (22%) were the most prevalent MRPs. Being >50 years (adjusted odds ratio (AOR) = 15.37, 95% confidence interval (CI) = 2.25–105.09, p = 0.005), treated with ≥5 medications (AOR = 7.00, 95% CI = 2.65–18.49, p < 0.001), and being stage III (AOR = 15.43, 95% CI = 2.92–81.47, p = 0.001) and stage IV (AOR = 8.41, 95% CI = 1.35–52.44, p = 0.023) were independent predictors of MRPs. Conclusion More than half of patients with cervical cancer had one or more MRPs. Being older, patients taking polypharmacy, stage III and IV patients were significantly associated with the development of MRPs. As most of the cervical patients experienced one or more MRPs, clinical pharmacy service should be strengthened to optimize drug therapy to reduce unwanted adverse events.

A review and metanalysis of metronomic oral single-agent cyclophosphamide for treating advanced ovarian carcinoma in the era of precision medicine

Objective Oral metronomic cyclophosphamide has been used as a single agent or in combination with other drugs for several solid tumors with interesting results in disease palliation and mild to moderate toxicity, notably in patients with recurrent epithelial ovarian cancer (EOC) progressing after systemic chemotherapy. In this paper, we report a review and a metanalysis of heterogeneous data published up to date. Data sources The literature search was restricted to single-agent MOC. The analysis was conducted through March 2023 by consulting PubMed, Embase, Google Scholar, and The Cochrane Library databases. Research string and Medical Subject Headings included “ovarian tumor,” “ovarian carcinoma,” or “ovarian cancer,” “fallopian tube cancer,” “primary peritoneal cancer,” “oral chemotherapy,” and “metronomic cyclophosphamide.” All articles were assessed for quality by at least two investigators independently, and a < 18 patients sample size cutoff was chosen as a lower limit with a Cohen's kappa statistical coefficient for accuracy and reliability. Metanalysis of selected papers was carried out according to a fixed model. Data summary The percentage of agreement between investigators on literature study selection was very high, reaching 96.9% with a Cohen's k of 0.929. MOC pooled objective response rate (ORR) and disease control rate for recurrent or platinum-refractory ovarian cancer were 18.8% (range 4–44%) and 36.2% (range 16–58.8%), respectively. The mean progressive-free survival and overall survival were 3.16 months (range 1.9 to 5.0 months) and 8.7 months (range 8 to 13 months), respectively. The fixed model metanalysis of selected studies showed a 16% median ORR (12–20% CI, p < 0.001). Conclusions Single-agent oral cyclophosphamide in EOC holds promise as a treatment option, even in the era of precision medicine. Genetic factors, such as DNA repair gene polymorphisms, may influence treatment response. Combining cyclophosphamide with biological agents such as PARP inhibitors or immunotherapy agents is an area of active investigation.

Real-world evidence of poly ADP-ribose polymerase inhibitors in the treatment of ovarian cancer: A systematic literature review

Objective The treatment landscape for ovarian cancer has shifted in recent years with the approval of poly ADP-ribose polymerase inhibitors in 2014. Most patients with ovarian cancer have advanced disease at diagnosis. Understanding how treatments for advanced disease work in real-world settings must be assessed to provide care for these patients. Therefore, the objective of this study was to locate and assess real-world studies measuring the safety and effectiveness of poly ADP-ribose polymerase inhibitors and analyze the results. Data sources: A targeted systematic literature review was conducted in April 2020 of PubMed/Medline. Inclusion criteria consisted of observational studies using real-world data of olaparib, rucaparib, or niraparib as an intervention in the treatment of ovarian cancer. In addition, studies needed to assess either clinical effectiveness or safety. Once studies were identified, we aimed to narratively describe the studies’ patient population, intervention effectiveness, and/or safety. Data summary: Our systematic review identified six studies assessing the real-world effectiveness and/or safety of poly ADP-ribose polymerase inhibitors, with five assessing olaparib, one assessing poly ADP-ribose polymerase inhibitors as a composite, and none assessing either niraparib or rucaparib. The median progression free survival in the real-world trials for olaparib ranged from 12.7 to 15.6 months. The median overall survival in the real-world trials for olaparib ranged from 30.9 to 35.4 months. Rates of treatment discontinuation due to adverse events for olaparib ranged from 4.4% to 12.5%. Conclusions The identified studies showed slightly higher, but comparable results for median progression free survival, median overall survival, and discontinuation due to adverse events compared to the respective randomized controlled trials.

Adherence and adverse events of intraperitoneal chemotherapy in optimally debulked ovarian cancer patients: Real-life study

Purpose Intraperitoneal with intravenous chemotherapy (IP/IV) is the recommended option for patients with stage III cancer with optimally debulked (<1 cm residual) disease based on randomized controlled trials and showing important improvements in overall survival and progression free survival. However, its application has not been largely adopted due to its difficult administration that requires a trained nurse staff. The aim of this work was to study the completion and the toxicity of an IP outpatient chemotherapy regimen in optimally debulked stage III ovarian cancer patients. Methods A single-center, retrospective observational study in women with stage III ovarian cancer following optimal cytoreductive surgery (<1 cm) followed by IP/IV chemotherapy from 2009 to 2017. The IP/IV regimen was as it follows: IV paclitaxel 175 mg/m 2 in 3 h, day 1; IP cisplatin (100 mg/m 2 —until December 2013—or 75 mg/m 2 ), day 2; IP paclitaxel 60 mg/m 2 , day 8, each 21 days for six cycles. Results A total of 60 patients received IP/IV regimen. Of these, 41 patients (68.3%) completed the six IP chemotherapy cycles and 51 (84.9%) completed four or more cycles. Most of the adverse events reported were non-hematological and G1-2. There was no difference neither in adherence nor in the frequency of adverse events between both cisplatin groups. Despite a high rate of adverse events, IP chemotherapy can be delivered with a high completion rate and manageable toxicity to patients with optimally debulked ovarian cancer.

Pharmacological issues concerning olaparib capsule and tablet formulations in treating ovarian cancer: Are they really the same drug?

Olaparib is a first-in-class PARP inhibitor that has demonstrated efficacy as maintenance therapy in patients with ovarian cancer. It has been approved as a capsule formulation and after the publication of data from SOLO2 study became available also as tablet formulation. Due to different pharmacokinetic properties, these different formulations cannot be considered bioequivalent nor interchangeable. The tablet formulation has improved bioavailability, reducing pill burden and offering a more convenient dosage regimen. Furthermore, olaparib tablet formulation had a manageable tolerability profile if compared to capsule one, with most of adverse events of mild or moderate severity. Under this light, olaparib tablet formulation is a useful maintenance strategy for recurrent, platinum-sensitive ovarian cancer, providing a more convenient dosing option than the capsule formulation.

Intraperitoneal paclitaxel and cisplatin compared with dose-dense paclitaxel and carboplatin for patients with stage III ovarian cancer

Introduction Patients diagnosed with stage III ovarian cancer are at high risk of recurrence and optimal adjuvant therapy is often debated. There is limited literature that directly compares intraperitoneal paclitaxel and cisplatin with dose-dense paclitaxel and carboplatin. Objectives The primary objective was to compare progression-free survival, overall survival, and tolerability of adjuvant intraperitoneal paclitaxel and cisplatin to dose-dense paclitaxel and carboplatin in stage III ovarian cancer patients. Methods A retrospective, IRB-approved, single center chart review was conducted reviewing adult patients with stage III ovarian cancer undergoing adjuvant intraperitoneal therapy or dose-dense therapy between 2010 and 2018. Results Eighty-two patients were included in the final analysis; 44 in the intraperitoneal group and 38 in the dose-dense group. Intraperitoneal therapy was not associated with a longer progression-free survival (35.4 vs. 31.1 months; P = 0.97). The duration of overall survival did not differ between intraperitoneal and dose-dense (56.3 vs. 54.5 months; P = 0.55). Dose reductions were less frequent with intraperitoneal than dose-dense (11.36% vs. 31.58%; P = 0.02). No difference in treatment delays (45.5% vs. 65.8%; P = 0.07), dose cancellations (59.1% vs. 57.9%; P = 0.91), supportive care additions (95.5% vs. 84.2%; P = 0.09), or therapy discontinuation (59.1% vs. 39.5%; P = 0.07) between groups was noted. Conclusions Intraperitoneal therapy with paclitaxel and cisplatin, as compared with dose-dense paclitaxel and carboplatin, did not prolong progression-free or overall survival in the adjuvant setting among stage III ovarian cancer patients. A trend towards decreased tolerability was noted with intraperitoneal therapy.

PARP-inhibitor potpourri: A comparative review of class safety, efficacy, and cost

Purpose To summarize similarities and differences in efficacy, safety, and cost of available PARP-inhibitors and offers pearls to distinguish subtle nuances between each agent to help guide therapy. Summary Currently, four PARP-inhibitors (olaparib, rucaparib, niraparib, and talazoparib) are FDA-approved, with olaparib, rucaparib, and niraparib approved for treatment and/or maintenance or ovarian cancer and olaparib and talazoparib approved for the treatment of recurrent metastatic BRCA-mutant, HER2-negative breast cancer. While the PARP-inhibitor class is generally are well-tolerated, each agent does possess a unique side-effect profile. Niraparib and talazoparib have more prominent hematologic adverse event profiles, while niraparib has an increased risk of cardiac events. In patients using other medications with known drug interactions, niraparib may be the preferred option for patients with ovarian cancer, and talazoparib may be the preferred option for patients with breast cancer because neither of these agents undergo hepatic metabolism. These agents also can incur large financial toxicities for patients, and olaparib currently has the broadest range of options for financial assistance. Conclusion Although these agents have similar approved indications, efficacy, and toxicity profiles, there are notable differences that may help direct choice of therapy and optimize treatment for patients. It is important to incorporate patient-specific factors to optimize PARP-inhibitor therapy for patients.

Bevacizumab-induced dysphonia: A case report with brief review of literature

Introduction Anti-angiogenic treatment in adjunct with chemotherapy is widely used for the treatment of various cancers. These agents inhibit vascular endothelial growth factor (VEGF) signaling thereby inhibiting tumor proliferation and invasion. Dysphonia, or voice changes, has been documented, but is an underreported side effect of anti-angiogenic agents. We report a case of intermittent dysphonia in a patient with metastatic, platinum-refractory ovarian cancer treated with bevacizumab. Case report A 48-year-old female with high grade mixed type ovarian adenocarcinoma and concurrent left sided breast cancer was transitioned to palliative therapy with gemcitabine-bevacizumab for her ovarian cancer. At a follow-up visit after three cycles of the new therapy, the patient complained of intermittent changes in her voice, describing periods of hoarseness or softness in her voice after the chemotherapy—sometimes to the point that her voice was inaudible. Management and outcome: A new pelvic thrombus was discovered upon assessment of the patient’s disease. Bevacizumab was held and she was referred to ear, nose, and throat evaluation for dysphonia. Laryngoscopic examination showed normal vocal cord, with normal movements and no lesion or necrosis. During subsequent follow-up, the patient reported improvement in her voice with no additional dysphonia. Discussion Vocal adverse effects of anti-VEGF agents have been documented in landmark trials and case reports; however, clinicians are often unaware of this rare side effect. Although VEGF-induced dysphonia may be rare and may not impede the patient’s quality of life in some cases, it is critical to acknowledge and not underestimate this adverse effect.