Phase I and Pharmacologic Study of the Combination of Paclitaxel, Cisplatin, and Topotecan Administered Intravenously Every 21 Days as First-Line Therapy in Patients With Advanced Ovarian Cancer

• Published in: Journal of clinical oncology Vol. 17; no. 3; pp. 747 - 755
• Main Authors: HERBEN, V. M. M, NANNAN PANDAY, V. R, TEN BOKKEL HUININK, W. W, RICHEL, D. J, SCHELLENS, J. H. M, VAN DER VANGE, N, ROSING, H, BEUSENBERG, F. D, HEARN, S, DOYLE, E, BEIJNEN, J. H
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-03-1999; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Blood Cell Count; Chemotherapy; Cisplatin - administration & dosage; Cisplatin - pharmacokinetics; Fatigue - chemically induced; Female; Granulocyte Colony-Stimulating Factor - administration & dosage; Humans; Infusions, Intravenous; Medical sciences; Middle Aged; Nausea - chemically induced; Neoplasm Staging; Neutropenia - chemically induced; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Paclitaxel - administration & dosage; Paclitaxel - pharmacokinetics; Pharmacology. Drug treatments; Thrombocytopenia - chemically induced; Topotecan - administration & dosage; Topotecan - pharmacokinetics; Antineoplastic agent; Carcinoma; Toxicity; Ovary; Granulocyte colony stimulating factor; Isomerases; Limit dose; Taxane derivatives; Paclitaxel; Complication; Advanced stage; Antimitotic; Platinum II Complexes; Human; Drug combination; Enzyme; Cytokine; DNA topoisomerase; Enzyme inhibitor; Topotecan; Malignant tumor; Cisplatin; Female genital diseases; Ovarian diseases; Chemotherapy; Treatment; Polypeptide; Phase I trial; Pharmacokinetics
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.1999.17.3.747

To evaluate the feasibility of administering topotecan in combination with paclitaxel and cisplatin without and with granulocyte colony-stimulating factor (G-CSF) support as first-line chemotherapy in women with incompletely resected stage III and stage IV ovarian carcinoma.
Starting doses were paclitaxel 110 mg/m2 administered over 24 hours (day 1), followed by cisplatin 50 mg/m2 over 3 hours (day 2) and topotecan 0.3 mg/m2/d over 30 minutes for 5 consecutive days (days 2 to 6). Treatment was repeated every 3 weeks. After encountering dose-limiting toxicities (DLTs) without G-CSF support, the maximum-tolerated dose was defined as 5 microg/kg of G-CSF subcutaneously starting on day 6.
Twenty-one patients received a total of 116 courses at four different dose levels. The DLT was neutropenia. At the first dose level, all six patients experienced grade 4 myelosuppression. G-CSF support permitted further dose escalation of cisplatin and topotecan. Nonhematologic toxicities, primarily fatigue, nausea/vomiting, and neurosensory neuropathy, were observed but were generally mild. Of 15 patients assessable for response, nine had a complete response, four achieved a partial response, and two had stable disease.
Neutropenia was the DLT of this combination of paclitaxel, cisplatin, and topotecan. The recommended phase II dose is paclitaxel 110 mg/m2 (day 1), followed by cisplatin 75 mg/m2 (day 2) and topotecan 0.3 mg/m2/d (days 2 to 6) with G-CSF support repeated every 3 weeks.