A phase I-II study of weekly cisplatin and gemcitabine with concurrent radiotherapy in locally advanced cervical carcinoma.
BACKGROUND
The purpose of this study was to determine the maximum-tolerated dose (MTD) and the antitumor activity of gemcitabine when administered in combination with concurrent cisplatin and radiotherapy in locally advanced cervical carcinoma (LACC).


METHODS
Patients with histologically confirmed LACC (International Federation of Gynecology and Obstetrics IIB-IVA), previously untreated, were eligible for entry in the study to receive radiotherapy and concomitant weekly chemotherapy with cisplatin 40 mg/m(2) and gemcitabine at increasing doses levels until the MTD was found.


RESULTS
Thirty-six patients were included. Sixteen patients were entered at four dose levels. The MTD was 150 mg/m(2) and the recommended dose of gemcitabine for phase II was 125 mg/m(2). Twenty additional patients were entered at this level. Toxicity at the recommended dose was acceptable with grade 3/4 toxicity in <20% of patients. Thirty-five of thirty-six patients (97.3%) achieved an objective response, 32 (88.8%) a complete response (CR) three a (8.3%) partial response and one (2.7%) stable disease. At a median follow-up of 26 months, 28 of 36 patients (77.7%) are in sustained complete remission and seven of 36 (19.4%) have relapsed. The 3-year disease-free and overall survival rates are 67% and 72%, respectively.


CONCLUSIONS
The association of cisplatin and gemcitabine with concurrent radiotherapy is active and well-tolerated in untreated LACC.
Zarbá
J J
JJ
GETICS, Yerba Buena, Tucumán, Argentina. jzarba@arnet.com.ar
Jaremtchuk
A V
AV
Gonzalez Jazey
P
P
Keropian
M
M
Castagnino
R
R
Mina
C
C
Arroyo
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011336:Probability; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine