title: A phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary.
abstract: We have conducted a disease specific phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary. This was done to take advantage of the cellular and molecular synergism between paclitaxel and DNA-damaging agents, with the hope of avoiding paclitaxel-cisplatin toxicities. Paclitaxel was given as a 24-hr CIVI, after which cyclophosphamide was given as a 60-min infusion. Cycles of therapy were repeated every 3 weeks; and granulocyte colony-simulating factor (G-CSF) was given in a "flexible" dosing fashion. Starting doses were 170 mg/m2 paclitaxel and 750 mg/m2 cyclophosphamide. Dose-limiting toxicity (DLT) was seen at the doses of 250 mg/m2 paclitaxel and 1250 mg/m2 cyclophosphamide. DLT was cumulative thrombocytopenia. There were six nonhematologic grade 3 or 4 toxicities experienced in the study. Eleven of 20 evaluable patients (55%) have achieved an objective response (4 CCR;7 PR). Three of four CCRs were confirmed by negative findings at peritoneoscopy. The median number of prior therapies was 2 (range 1-4) and 17 individuals had platinum-refractory disease. We conclude that paclitaxel followed by cyclophosphamide is an active combination in recurrent ovarian cancer and that further study is needed to determine if this combination is truly better than paclitaxel alone.
authors.affiliation: Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: E
authors.initials: E
authors.lastname: Reed
authors.forename: G
authors.initials: G
authors.lastname: Sarosy
authors.forename: E
authors.initials: E
authors.lastname: Kohn
authors.forename: M
authors.initials: M
authors.lastname: Christian
authors.forename: C J
authors.initials: CJ
authors.lastname: Link
authors.forename: B
authors.initials: B
authors.lastname: Goldspiel
authors.forename: P
authors.initials: P
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Jacob
authors.forename: M
authors.initials: M
authors.lastname: Maher
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D003520:Cyclophosphamide; D017239:Paclitaxel