Phase II study of a combination of cisplatin, all-trans-retinoic acid and interferon-alpha in squamous cell carcinoma: clinical results and pharmacokinetics.
Preclinical and clinical data suggest a certain antitumor efficacy for combination of retinoids, cytokines and cytotoxic compounds.


METHODS
Between November 1994 and October 1996, 38 patients with advanced squamous cell carcinoma were enrolled in a phase II study to investigate an association of low-dose all-trans-retinoic acid (tRA) (40 mg/m2/day, 84 days), interferon-alpha (IFN-alpha) (6.10(6) UI/day, 84 days s.c.) and cisplatin (40 mg/m2/day, day 1, 28 and 56, i.v.). A Pharmacokinetic evaluation was performed on 12 patients.


RESULTS
The incidence of grade 3/4 hematologic toxicities was moderate (< 20%). Extra hematological toxicities were frequent but easily manageable and not life threatening. However, treatment delivery was poor since only 6 patients (16%) received full therapy. Seven objective responses were observed (21%), suggesting some degree of synergism between tRA, IFN-alpha and cisplatin. Interestingly, continuous tRA treatment in combination with IFN-alpha and cisplatin did not induce a significant decrease in plasma levels, as had been previously described.


CONCLUSIONS
Regarding the short median response duration and the frequency of toxic events, this regimen should no longer be recommended in pretreated patients with advanced disease. However, the consistent response rate reported here may warrant further investigation in an early setting.
Goncalves
A
A
Department of Medicine, Institut Paoli-Calmettes, 232 Bd Sainte Marguerite, 13273 Marseille, France.
Camerlo
J
J
Bun
H
H
Gravis
G
G
Genre
D
D
Bertucci
F
F
Resbeut
M
M
Pech-Gourg
F
F
Durand
A
A
Maraninchi
D
D
Viens
P
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014212:Tretinoin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D016898:Interferon-alpha; D014212:Tretinoin; D002945:Cisplatin