Retinoids, cisplatin and interferon-alpha in recurrent or metastatic cervical squamous cell carcinoma: clinical results of 2 phase II trials.
BACKGROUND
There is no standard treatment for inoperable recurrent or metastatic cancer of the uterine cervix. Retinoids and interferon, in combination with cytotoxic compounds, have been shown to be active in squamous cell carcinoma (SCC). This phase II trial sought to estimate the response rate and the tolerance to a 3-month treatment combining cisplatin, interferon-alpha (IFN-alpha) and all-trans-retinoic (tRA) or 13 cis retinoic acid (13Cis), in women with recurrent or metastatic cervical SCC.


METHODS
Between November 1994 and October 1996, 33 patients, who had previously received aggressive treatment, and with metastatic and/or bulky disease were enrolled: 22 received tRA(40 mg/m(2)/day), 11 received 13Cis (1 mg/kg/day) in combination with IFN-alpha (6.106 UI/day SC) for 84 days plus cisplatin (40 mg/m(2)IV, days 1, 28 and 56).


RESULTS
All patients were evaluable for response and/or toxicity. Toxicities were easily manageable and were never life-threatening, with major grade 3/4 vomiting (54%) and asthenia (54%). Seventeen patients (52%) stopped or reduced treatment because of toxicity or progression. Six objective responses (18%) were observed. No complete response was recorded. Median response duration was 4 months. Time to progression was 9 months [range 3.3 to 20.9] for responders and 7 months [range 1.7 to 32] for all patients.


CONCLUSIONS
Regarding toxicity, this regimen should no longer be recommended in previously treated, advanced uterine SCC. However, the consistent response rate reported here may warrant further investigations in an early setting. Retinoid-based treatment with cytokines remains a promising field of research.
Braud
Anne-Chantal
AC
Department of Medicine, Institut Paoli-Calmettes, 232 boulevard Sainte-Marguerite, 13273 Marseille Cedex 9, France.
Gonzague
Laurence
L
Bertucci
François
F
Genre
Dominique
D
Camerlo
Jacques
J
Gravis
Gwenaelle
G
Goncalves
Anthony
A
Moutardier
Vincent
V
Viret
Frédéric
F
Maraninchi
Dominique
D
Viens
Patrice
P
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D018675:Toxicity Tests; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D016898:Interferon-alpha; D014212:Tretinoin; D015474:Isotretinoin; D002945:Cisplatin