Phase I and pharmacological study of an oxaliplatin and carboplatin combination in advanced malignancies.
BACKGROUND
Phase I and pharmacokinetic study to determine the maximal tolerated dose and the recommended dose, as well as the optimal sequence of a carboplatin/oxaliplatin combination delivered every 3 weeks.


METHODS
Patients received either carboplatin [area under the curve (AUC)-based individually calculated dose (starting dose AUC 4 mg.min/ml), 1 h intravenous (i.v.) infusion] followed by oxaliplatin (110 mg/m(2), 2 h i.v. infusion), every 3 weeks, or the reverse sequence.


RESULTS
Sixteen patients were included and only one dose level was assessed. In group A, 10 patients received 23 cycles of carboplatin followed by oxaliplatin. In group B, 6 patients received 20 cycles with the reverse sequence. Delayed recovery from hematological toxicities was treatment-limiting, with mainly moderate thrombocytopenia and neutropenia as dose-limiting toxicities for group A (5 of 10 patients for each) and thrombocytopenia for group B (3 of 6 patients). No febrile neutropenia or grade 3/4 non-hematological toxicity occurred. Pharmacokinetic analysis showed similar mean total platinum AUCs for the two groups: 37.2 +/- 13.7 and 33.6 +/- 9.9 mg.h/l, respectively. One complete response and two partial responses (World Health Organization-International Union Against Cancer criteria, response rate 18.8%) were seen in ovarian, Fallopian and neuroendocrine carcinomas, respectively.


CONCLUSIONS
This platinum combination appears feasible and active at the dose of AUC 4 mg.min/ml for carboplatin (Chatelut formula) and oxaliplatin 110 mg/m(2); however, it does not allow a significant increase in platinum dose-intensity delivery.
Mita
C
C
Institut Claudius Regaud, and Université Paul Sabatier, Toulouse, France. amita@idd.org
Chatelut
E
E
Bekradda
M
M
Soulié
P
P
Canal
P
P
Misset
J-L
JL
Cvitkovic
E
E
Bugat
R
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000077150:Oxaliplatin; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin