title: Interim results of a randomized trial of mitomycin C as an adjunct to radical radiotherapy in the treatment of locally advanced squamous-cell carcinoma of the cervix.
abstract: The purpose of this study was to determine the efficacy of mitomycin C as an adjunct to radiotherapy for the treatment of locally advanced cervix cancer. Patients with squamous-cell carcinoma of the cervix, stages IB2-IVA, were randomized to receive radiotherapy alone or radiotherapy with concomitant mitomycin C. An initial cohort of 160 patients, having a mean follow-up of 46 months, is analyzed. Intravenous mitomycin C, 15 mg/M(2), was given on the first and sixth week of radiotherapy. The 78 patients in the radiotherapy with mitomycin C group and 82 patients in the radiotherapy alone group have a comparable distribution by age and stage (mean age 47 years; stage IB 3%, IIA 11%, IIB 48%, IIIA 1%, IIIB 36%, IVA 3%). The four-year actuarial survival rates for radiotherapy with mitomycin C and radiotherapy alone were 72% and 56%, respectively (P = 0.13). The four-year actuarial disease-free survival rates for radiotherapy with mitomycin C and radiotherapy alone were 71% and 44%, respectively, a statistically significant difference (P = 0.01). The four-year actuarial local recurrence-free survival rates for patients receiving radiotherapy with mitomycin C and radiotherapy alone were 78% and 63%, respectively (P = 0.11). Differences in four-year distant recurrence-free survival between radiotherapy plus mitomycin C and radiotherapy alone were significantly different at 85% vs. 61% (P = 0.01); this analysis is not adjusted for local failure. On subgroup analysis, stage III-IVA patients had a four-year actuarial disease-free survival of 75% for radiotherapy plus mitomycin C compared with 35% for radiotherapy alone (P = 0.03). There were no treatment- related deaths. Mild hematologic toxicity was seen only in the group treated with mitomycin C. No excess in non-hematologic toxicity has been observed thus far with combined mitomycin C and radiotherapy. In this open phase III trial of mitomycin C as an adjunct to radical radiotherapy for squamous-cell carcinoma of the cervix, there were minimal hematologic effects and no increase in acute radiation reactions. A statistically significant difference in favor of patients receiving mitomycin C is shown for disease-free survival. Thus far, there are trends in favor of those patients receiving mitomycin C for survival and local control. Patients with more advanced stage disease, predominantly stage IIIB, appear to have the most benefit. These preliminary results support the hypothesis that targeting hypoxic cells may lead to a therapeutic enhancement in the radiotherapy of cervix cancer. This trial continues to accrue patients and follow-up data. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 206-223 (2000).
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520-8040, USA. kenneth.roberts@yale.edu
authors.forename: K B
authors.initials: KB
authors.lastname: Roberts
authors.forename: N
authors.initials: N
authors.lastname: Urdaneta
authors.forename: R
authors.initials: R
authors.lastname: Vera
authors.forename: A
authors.initials: A
authors.lastname: Vera
authors.forename: E
authors.initials: E
authors.lastname: Gutierrez
authors.forename: Y
authors.initials: Y
authors.lastname: Aguilar
authors.forename: S
authors.initials: S
authors.lastname: Ott
authors.forename: I
authors.initials: I
authors.lastname: Medina
authors.forename: P
authors.initials: P
authors.lastname: Sempere
authors.forename: S
authors.initials: S
authors.lastname: Rockwell
authors.forename: A C
authors.initials: AC
authors.lastname: Sartorelli
authors.forename: D B
authors.initials: DB
authors.lastname: Fischer
authors.forename: J J
authors.initials: JJ
authors.lastname: Fischer
mesh_terms: D000206:Actuarial Analysis; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000009:adverse effects / Q000627:therapeutic use*; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin