Cisplatin-paclitaxel weekly schedule in advanced solid tumors: a phase I study.
OBJECTIVE
The objective of our study was to determine the maximum tolerable doses (MTDs) of both paclitaxel and cisplatin when given in a weekly schedule alone or simultaneously with G-CSF in advanced solid neoplasms.


METHODS
Patients with advanced cancer either chemotherapy-naive or resistant to standard treatments received paclitaxel in a three-hour infusion followed by cisplatin, with or without the addition of r-HuG-CSF (5 micrograms/kg s.c. days three to five). The starting doses of CDDP and paclitaxel were 25 mg/m2/week and 45 mg/m2/week, respectively. During the first six courses the dosages of the two drugs were alternately escalated by 20% (CDDP = 5 mg/m2/week, and paclitaxel 10 mg/m2/week) at each step until the appearance of dose-limiting toxicity (DLT) in one-third or more of the patients enrolled in that cohort.


RESULTS
Fifty-five patients with cancer (16 lung, 16 breast, 11 ovarian, 7 head and neck, 1 renal, 1 esophageal, 1 cervical, 1 soft-tissue sarcoma, and 1 of unknown primary), 25 of whom were pretreated, were entered into the study. A total of 439 weekly courses were delivered. In chemotherapy-naïve patients, the MTDs of cisplatin and paclitaxel were 30 mg/m2/week and 65 mg/m2/week, respectively, in the absence of G-CSF support, which increased to 40 mg/m2/week and 85 mg/m2/week, respectively, when G-CSF was given. There were no toxic deaths in this study. Neutropenia was the main dose-limiting toxicity (100/439 courses), but was seldom severe. Neurotoxicity was quite frequent (18 of 55 patients for the total of 88 courses) but never dose-limiting. It was more frequent and clinically relevant in cisplatin-pretreated patients. Overall 18 patients (eight ovarian, five breast, three lung, and two head and neck) achieved objective responses.


CONCLUSIONS
The cisplatin-paclitaxel weekly administration seems a safe, practical and effective therapeutical approach in patients with advanced solid neoplasms. Large phase II trials are warranted to accurately define the efficacy of this schedule in cisplatin-paclitaxel sensitive tumors.
Frasci
G
G
Division of Medical Oncology A, National Tumor Institute of Naples, Italy.
Comella
P
P
Parziale
A
A
Casaretti
R
R
Daponte
A
A
Gravina
A
A
De Rosa
L
L
Gallipoli
A
A
Comella
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011994:Recombinant Proteins; D019233:Retreatment
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel; D002945:Cisplatin