Phase II study of three-dimensional conformal radiotherapy and concurrent mitomycin-C, vinblastine, and cisplatin chemotherapy for Stage III locally advanced, unresectable, non-small-cell lung cancer.
OBJECTIVE
To evaluate the feasibility, treatment outcome, and toxicity of hyperfractionated three-dimensional conformal radiotherapy (CRT) and concurrent mitomycin-C, vinblastine, and cisplatin (MVP) chemotherapy in locally advanced, unresectable, Stage III non-small-cell lung cancer (NSCLC).


METHODS
Between August 1993 and December 1996, 161 patients with unresectable Stage III NSCLC were entered into this trial, and 146 (91%) completed the treatment. Hyperfractionated RT was given to a total dose of 64.8-70 Gy (1.2 Gy/fraction, b.i.d.) with two cycles of concurrent MVP chemotherapy (mitomycin-C 6 mg/m(2) on Days 2 and 29, vinblastine 6 mg/m(2) on Days 2 and 29, and cisplatin 60 mg/m(2) on Days 1 and 28). Of the 146 patients who completed the treatment, 78 received noncoplanar three-dimensional CRT using 4-6 fields and 17 received coplanar-segmented CRT. The clinical tumor response was assessed 1 month after RT completion by CT. Toxicity was graded using the Southwestern Oncology Group criteria. The normal tissue complication probability for the lung was calculated to determine the correlation with radiation pneumonitis, if any. Nineteen (13%) had Stage IIIA and 127 (87%) had IIIB disease, including 16 patients with pleural effusion and 20 with supraclavicular lymph node metastasis.


RESULTS
The response rate was 75%, composed of 22% complete responders and 53% partial responders. With a minimal follow-up of 45 months, the overall survival rate was 51.2% at 1 year, 25.1% at 2 years, and 14.8% at 5 years; the median survival was 12 months. Patients achieving a complete response (n = 32) had a 2-year overall survival rate of 49.8% and a 5-year survival rate of 39.2% compared with 22.5% and 11.4%, respectively, for the partial responders (n = 78; p = 0.0001). The actuarial local progression-free survival rate for all patients was 65.4% at 1 year, 42.1% at 2 years, and 36.3% at 4 years, and the actuarial distant-free survival rate was 65.4% at 1 year, 42.1% at 2 years, and 36.2% at 5 years. Severe weight loss (>10%) occurred in 20 (13.7%) of the 146 patients during treatment, 42 patients (29%) developed radiation pneumonitis (29 Grade 1 and 13 Grade 2). The average normal tissue complication probability value of the patients who had radiation pneumonitis was significantly greater than that of patients without pneumonitis (66.0% vs. 26.4%). Four patients died of treatment-related toxicity.


CONCLUSIONS
Hyperfractionated three-dimensional CRT and concurrent chemotherapy, as described here, is a well-tolerated regimen with acceptable toxicity. More effective treatment schemes are required to improve local disease control and overall survival.
Lee
Sang-wook
SW
Department of Radiation Oncology, Asan Medical Center, University of Ulsan Medical College, Songpa-Ku, Seoul, South Korea.
Choi
Eun Kyung
EK
Lee
Jung Shin
JS
Lee
Sang Do
SD
Suh
Cheolwon
C
Kim
Sang-We
SW
Kim
Woo Sung
WS
Ahn
Seung Do
SD
Yi
Byong Yong
BY
Kim
Jong Hoon
JH
Noh
Young Ju
YJ
Kim
Su Ssan
SS
Koh
Younsuck
Y
Kim
Dong Soon
DS
Kim
Won-Dong
WD
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D008937:Mitomycins; D014747:Vinblastine; D002945:Cisplatin