Phase I trial of escalating doses of paclitaxel combined with fixed doses of cisplatin and doxorubicin in advanced endometrial cancer and other gynecologic malignancies: A Gynecologic Oncology Group Study

Purpose: The primary objective of this phase I trial was to determine the f easibility of administering ct combination of paclitaxel, cisplatin, and do xorubicin with or without granulocyte colony-stimulating factor (G-CSF) in patients with advanced endometrial and other gynecologic cancers. Patients and Methods: Patients were chemotherapy-naive. Doxorubicin was adm inistered as a brief infusion, paclitaxel for 3 hours, and cisplatin for 60 minutes. Treatments were repeated every 3 weeks. For most dose levels, the cisplatin and doxorubicin were fixed at 60 mg/m(2) and 45 mg/m(2), whereas the paclitaxel was escalated in successive cohorts from 90 to 250 mg/m(2). Patients who had received previous radiotherapy to the whole pelvis were e scalated separately from those who had not. Results: Eighty patients received 320 cycles of therapy. When G-CSF was not used, myelosuppression prevented escalation beyond the starting dose for p atients with or without previous pelvic radiotherapy. When G-CSF was added, neurotoxicity became dose-limiting for both groups. Ten patients were remo ved from the study for asymptomatic declines in ejection fraction, but no s ymptomatic congestive heart failure was observed. Major antitumor responses occurred in 46% of: patients (six of 13) with measurable endometrial carci noma and 50% of patients (eight of 16) with measurable cervical carcinoma. Conclusion: The combination of paclitaxel, doxorubicin, and cisplatin at re levant single-agent doses is active and feasible with the addition of G-CSF . A regimen of: cisplatin 60 mg/m(2), doxorubicin 45 mg/m(2), and paclitaxe l 160 mg/m(2) with G-CSF support is recommended for further testing.