Phase I-II trial of preoperative chemoradiation in locally advanced cervical carcinoma.
BACKGROUND
5-Fluorouracil and cisplatin are characterized by in vitro synergism as well as radiosensitization. A phase I-II study was carried out on patients with invasive cervical carcinoma (FIGO IIB-IIIA) undergoing concomitant chemoradiation with 5-fluorouracil and cisplatin followed by radical surgery.


METHODS
Twenty-six patients of 53 years median age, 24 with IIB tumor and 2 with IIIA tumor, all with squamous carcinoma, entered the study. The chemoradiation protocol included external radiotherapy to the pelvis: 39.6 Gy (180 cGy/daily); 5-fluorouracil: 1 g/m(2)/daily, in continuous intravenous infusion days 1-4 and 27-30; cisplatin: 20 mg/m(2)/daily days 1-4 and 27-30. Four weeks after the end of chemoradiotherapy, patients underwent restaging and then radical surgery with pelvic and lumboaortic lymphadenectomy.


RESULTS
Twenty-six patients are evaluable for acute toxicity and 24 are evaluable for objective and pathologic response. Grade 3-4 thrombocytopenia or leukopenia was observed in 6 patients and grade 3 acute gastrointestinal toxicity in 3. After chemoradiation CR and PR were observed in 64 and 36% of cases, respectively (CR + PR = 100%). Two patients were excluded from surgery for other diseases. The remaining 24 patients were operated on; 23/24 patients showed negative section margins. The histology of the surgical specimen showed the absence of disease in 13 patients (54.2%), microscopic residual tumor in 4 patients (16.6%), residual disease </=1 cm in 5 patients, and residual disease >1 cm in 2 patients. Median follow up was 33 months. Two-year actuarial local control was 91.7%.


CONCLUSIONS
This study showed a particularly high rate of pathologic responses (complete + Tmic: 70.8%) and local control (2 years = 91.7%) in patients with advanced cervical cancer undergoing moderate doses of radiotherapy with concomitant chemotherapy followed by radical surgery.
Mancuso
S
S
Gynecology Department, Radiation Therapy Department, Radiology Department, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, Rome, 00168, Italy.
Smaniotto
D
D
Benedetti Panici
P
P
Favale
B
B
Greggi
S
S
Manfredi
R
R
Margariti
P A
PA
Morganti
A G
AG
Scambia
G
G
Tortoreto
F
F
Valentini
V
V
Cellini
N
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009367:Neoplasm Staging; D010349:Patient Compliance; D011300:Preoperative Care; D011379:Prognosis; D011859:Radiography; D011878:Radiotherapy / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000601:surgery
D002945:Cisplatin; D005472:Fluorouracil