Phase II study of a combination of low-dose cisplatin with 13-cis-retinoic acid and interferon-alpha in patients with advanced head and neck squamous cell carcinoma.
Preclinical and clinical data have suggested antitumor efficacy in squamous cell carcinoma (SCC) of interferon (IFN)-alpha and 13-cis-retinoic acid (13-c-RA) as single agent with greater activity in combination. Cisplatin was added to potentiate activity. Twenty-three patients with pretreated advanced or metastatic head and neck squamous cell carcinoma were given a combination of IFN-alpha (6 x 10(6) U/day, 84 days s.c.), 13-c-RA (1 mg/kg/day, 84 days) and cisplatin (40 mg/kg/day, day 1, 28 and 56). Seventeen patients had discontinuation of treatment and three patients received overall treatment without dose reduction. Hematological toxicity was more frequent; only three patients experiencing grade 3 or higher extra-hematological toxicity. Four out of 14 evaluable patients were in response, with one in complete pathological response. Median duration of response was 6 months with a 9 month median survival. Association of IFN-alpha, 13-c-RA and cisplatin induces modest but definite antitumor activity with moderate and manageable toxicity. Further studies of different combination modality therapy with chemotherapy and differentiating agents need to be performed in less pretreated patients.
Gravis
G
G
Medical Oncology Department, Institut Paoli-Calmettes, Marseille, France. oncomed@marseille.fnclcc.fr
Pech-Gourgh
F
F
Viens
P
P
Alzieu
C
C
Camerlo
J
J
Oziel-Taieb
S
S
Jausseran
M
M
Maraninchi
D
D
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013997:Time Factors; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015474:Isotretinoin; D002945:Cisplatin