[Study of vinorelbine (V) combined with hexamethylmelamine (H) (combination V-H) in adenocarcinoma of the ovary: results a phase I-IIA trial, NHO-88, of ARTAC "ovarian" group].
The lack of decisive progress in ovarian cancer chemotherapy in recent years led the ARTAC "Ovary" group to initiate a study based on the hypothesis of collateral sensitivities. In this phase I-II trial, NHO-88, the V-H combination (associating vinorelbine (VNB) and hexamethylmelamine (HMM) was studied in patients with advanced ovarian adenocarcinomas, most of which had become resistant to previous chemotherapy. The aim of the study was to find an active combination without complete cross resistance with first-line platinum salt based combinations, such as CAP, FAP or CACb-300. A pilot feasibility study was first carried out to determine the maximum tolerated weekly dose (MTWD) of VNB (20 mg/m2/week), HMM being administered per os on days 1-14 of every 28-day cycle at a standard dose of 250 mg/m2/day. An open phase II-A study was further carried out according to a 2-step sequential analysis method for phase II clinical trials. We observed: 1), a good tolerance of the V-H combination apart from frequent neutropenia; 2), a response rate of 35% (95% confidence interval: 23-47%); 3), a median response duration of 4 months (range: 1-7 months); 4), in some cases, the absence of a complete cross-resistance between the V-H regimen and the previously administered platinum-based combinations. These results, which are currently being validated (phase II-B ongoing), constitute the first step in the search for active systems of sequential or alternate chemotherapeutic regimens for the treatment of advanced carcinomas.
Pinon
G
G
Polyclinique de Courlancy, Reims, France.
Pinel
M C
MC
Goudier
M J
MJ
Coiffier
B
B
Filippi
M H
MH
Goupil
A
A
Roullet
B
B
Facchini
T
T
Mignot
L
L
Tresca
P
P
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D006585:Altretamine / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004341:Drug Evaluation; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016879:Salvage Therapy; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014747:Vinblastine; D000077235:Vinorelbine; D006585:Altretamine
Etude de la vinorelbine (V) associée à l'hexaméthylmélamine (H) (combinaison V-H) dans les adénocarcinomes de l'ovaire: résultats d'un essai phase I-IIA, NHO-88, du groupe "ovaire" de l'ARTAC.