Interest in an original methodology to define the optimal dosage of interferon-alpha-2a in metastatic melanoma patients.
Interferon-α-2a (IFNa) has proven antitumor activity in a variety of neoplastic diseases, but no clear modality of administration has been validated. The aim of our study was to estimate the optimal dose of continuous subcutaneous administration of IFNa in stage IV metastatic melanoma patients. An innovative dose-finding approach, combining phase I and phase II trials, was planned to evaluate the toxicity and efficacy of four dose levels of IFNa (3, 6, 9, and 12 MIU/day). Sixteen patients were enrolled in this study. Three patients were treated according to the dose-allocation rule with IFNa at 3 MIU/day, nine patients at 6 MIU/day, and four patients at 9 MIU/day. Dose-limiting toxicities were grade 3 in five patients (three at a dose level of 6 MIU/day and two at a dose level of 9 MIU/day). Four clinically relevant responses were obtained, one at dose level 3 MIU/day, one at a dose level of 6 MIU/day, and two at a dose level of 9 MIU/day. The three final responses, at dose levels of 6 and 9 MIU/day, were associated with a dose-limiting toxicity. A dose level of 6 MIU/day was well tolerated but did not reach the desired efficacy target of 20%, and a dose level of 9 MIU/day was estimated to be too toxic. This original dose-finding methodology made it possible to estimate the rate of toxicity and efficacy in a small sample of patients without toxicity associated with each dose level.
Centre d'Investigations Cliniques, Hôpital Saint Louis, 1, Avenue Claude Vellefaux, 75010 Paris, France. sarah.zohar@sls.aphp.fr
Sarah
S
Zohar
Jacques
J
Medioni
Céleste
C
Lebbé
Marie-Françoise
MF
Avril
Delphine
D
Kerob
Pirayeh
P
Eftekhari
Anne
A
Driheme
Karine Celli
KC
Lebras
Heriberto
H
Bruzzoni-Giovanelli
Vincent
V
Levy
Sylvie
S
Chevret
Fabien
F
Calvo
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D016898:Interferon-alpha