Chemoradiation with concomitant boost followed by radical surgery in locally advanced cervical cancer: a dose-escalation study.
OBJECTIVE
Aim of this study is to evaluate the feasibility of an accelerated fractionation radiotherapy by concomitant boost in locally advanced cervical cancer patients, to explore the maximum tolerated dose (MTD) of radiation through a dose-escalation scheme, and to verify if increasing the radiation dose would result in a higher rate of pathologic complete response.


METHODS
During the first and the last week of treatment, a combination of cisplatin (20 mg/mq/d, IV, days 1-4) and 5-fluorouracil (1 g/mq/d, continuous venous infusion, days 1-4) was administered. The dose escalation of external radiotherapy was delivered on the primary tumor, using the concomitant boost technique (CB, 90 cGy per fraction), delivering 3 different dose levels: (1) 1 weekly boost for a total dose of 4320 cGy; (2) 2 weekly boosts, total dose 4680 cGy; (3) 3 weekly boosts, total dose of 5040 cGy.


RESULTS
Eighteen patients were submitted to a radiochemotherapeutic schedule of 3960 cGy in 22 fractions on pelvic lymph nodal stations. The MTD of radiation was not reached, being the only toxicities registered neutropenia G3 (n = 4), thrombocytopenia G3 (n = 1), stomatitis G3 (n = 1), diarrhea G3 (n = 2) easily managed. Six weeks after the end of radiochemotherapy, 17 patients were submitted to radical surgery, and are therefore evaluable for pathologic response. Among them, 15 complete remissions (88.2%, including 3 microscopical partial response), 1 partial response (5.9%), and 1 progression (5.9%) have been observed.


CONCLUSIONS
These results demonstrate, even if in a small study, that this regimen of concurrent chemoradiation followed by radical surgery is well tolerated.
Cellini
Numa
N
Department of Radiotherapy, Catholic University of the Sacred Heart, Campobasso, Italy.
Smaniotto
Daniela
D
Scambia
Giovanni
G
Luzi
Stefano
S
Balducci
Mario
M
Ferrandina
Gabriella
G
Corvari
Barbara
B
Margariti
Pasquale A
PA
Valentini
Vincenzo
V
D'Agostino
Giuseppe
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
D002945:Cisplatin; D005472:Fluorouracil