First-line Cisplatin Chemotherapy Research Articles

Hörverlust durch Hochdosis-Carboplatintherapie

Carboplatin is regarded as a non-ototoxic or low-grade ototoxic chemotherapeutic agent. We report on three patients with a recurrence of testicular cancer after cisplatin chemotherapy who suffered hearing loss after subsequent high-dose carboplatin therapy. Audiometry demonstrated carboplatin-induced hearing loss primarily in the mid-range and high frequencies up to 45 dB at 3 kHz and up to 55 dB at 8 kHz. In two of three patients, transitory-evoked otoacoustic emissions were absent after carboplatin therapy. Following first-line cisplatin chemotherapy, salvage treatment with high-dose carboplatin can generate hearing loss in the middle and high frequencies.

Phase II trial of intraperitoneal carboplatin in ovarian carcinoma patients with macroscopic residual disease at second-look laparotomy: A multicentre study of the French Fédération Nationale des Centres de Lutte Contre le Cancer

Because of its antitumour activity and its pharmacological advantage when administered by the intraperitoneal route, carboplatin was studied in a phase II multicentric trial. The aim of the study was to determine the response rate and the toxicity of carboplatin administered intraperitoneally and to determine if pathological complete response could be attained in women with macroscopic residual ovarian cancer at second-look laparotomy after intravenous cisplatin chemotherapy. Twenty-nine patients with macroscopical residual disease after intravenous cisplatin-based chemotherapy at second-look laparotomy, were treated at that time with 300 mg/m2 of carboplatin administered in the abdominal cavity every four weeks for six cycles. In instances of negative findings at physical and CT scan examination, laparotomy evaluation was performed and the catheter was removed. The dose of carboplatin was increased or decreased according to hematological toxicity. Efficacy is evaluable in 25 pts: 2 pts had pathological complete responses and 1 pt had microscopic disease (12% response rate of evaluable patients). Toxicity is evaluable for 135 cycles in 29 patients. No grade 4 hematological toxicity was observed, 2 pts had grade 3 leukopenia and 3 pts had grade 3 thrombocytopenia; grade 3 vomiting was observed in 11% of cycles. No peritoneal complication was observed; catheter dysfunction occurred after the first cycle in one patient who refused a surgical procedure to remove the catheter and to pursue treatment. Intraperitoneal carboplatin demonstrates efficacy in patients with macroscopical residual disease at second-look laparotomy after first-line cisplatin chemotherapy. The recommended dose for further studies is 300 mg/m2 administered every 4 weeks. A low response rate does not favour a randomised study.

Cisplatin, etoposide, and ifosfamide salvage therapy for refractory or relapsing germ cell carcinoma.

Thirty patients with metastatic progressive germ cell carcinoma who failed to be cured with first-line cisplatin chemotherapy were treated with a salvage regimen consisting of cisplatin 20 mg/m2, etoposide 100 mg/m2, and ifosfamide 1.2 g/m2 (PEI) intravenously (IV), days 1 to 5 every 3 weeks. Ten patients (33%) were tumor-free at the end of therapy. Complete response (CR) was achieved with chemotherapy alone in four patients and with additional surgery in six patients (two necroses, two mature teratomas, two carcinomas). Six patients (20%) had normalization of tumor markers but unresectable residual disease (Rm-), and the remaining 14 patients (46%) failed to respond. Of 10 patients with CR, nine (90%) relapsed again (eight carcinomas, one mature teratoma). The median duration of CR was 3.5 months. The median survival of the whole group was 311 days (range, 110 to 996+). Currently, seven of 30 patients are alive, and five of them are without signs of progressive tumor. The response to prior cisplatin therapy predicted for response and survival after PEI salvage therapy. Of 14 patients with prior CR, eight (57%) achieved a second CR compared with one of 11 (9%) with prior unfavorable response (P = .039). The median survival for patients with prior favorable response was 400 days, compared with 251 days for patients with prior unfavorable response (P less than .001). Myelosuppression was dose-limiting, with leukopenia greater than grade 2 in 84% and thrombocytopenia greater than grade 2 in 51% of all cycles. This three-drug regimen can induce a second CR in one third of patients with relapsed or refractory germ cell carcinoma. Only those patients with prior favorable responses can expect to be cured by this salvage regimen, while patients with prior unfavorable response should be considered for alternative salvage approaches.