Rosalaura Villarreal-González

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.

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.

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.