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Title: Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis

Abstract

Sequential hemibody irradiation (SHB) was integrated with combination chemotherapy and local irradiation (LRT) in the induction and consolidation phases of a therapeutic protocol for small cell lung carcinoma (SCLC). Forty-one previously untreated patients were entered into this program. Among 38 evaluable patients (20 with limited disease (LD) and 18 with extensive disease (ED)), the overall response rate was 63% (90% in LD and 33% in ED patients). The estimated overall survival is 8.1 months. The major toxicity has been myelosuppression - especially thrombocytopenia. The frequency of previously described acute radiation syndromes and radiation pneumonitis associated with hemibody irradiation have been substantially decreased at the current dosage with premedication and shielding techniques.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Wake Forest Univ., Winston-Salem, NC
OSTI Identifier:
5548340
Resource Type:
Journal Article
Resource Relation:
Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States); Journal Volume: 11:3
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 62 RADIOLOGY AND NUCLEAR MEDICINE; DIARRHEA; RADIOINDUCTION; IMMUNOSUPPRESSION; PNEUMONITIS; RADIOTHERAPY; SIDE EFFECTS; CARCINOMAS; CHEMOTHERAPY; DOXORUBICIN; ENDOXAN; LUNGS; ONCOVIN; PARTIAL BODY IRRADIATION; PATIENTS; ALKALOIDS; ALKYLATING AGENTS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; BODY; DISEASES; DRUGS; EXTERNAL IRRADIATION; IMMUNOSUPPRESSIVE DRUGS; IRRADIATION; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; ORGANS; RADIOLOGY; RESPIRATORY SYSTEM; SYMPTOMS; THERAPY; 560151* - Radiation Effects on Animals- Man; 550603 - Medicine- External Radiation in Therapy- (1980-)

Citation Formats

Powell, B.L., Jackson, D.V. Jr., Scarantino, C.W., Pope, E., Choplin, R., Craig, J.B., Atkins, J.N., Cooper, M.R., Hopkins, J.O., and McMahan, R.. Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis. United States: N. p., 1985. Web. doi:10.1016/0360-3016(85)90175-0.
Powell, B.L., Jackson, D.V. Jr., Scarantino, C.W., Pope, E., Choplin, R., Craig, J.B., Atkins, J.N., Cooper, M.R., Hopkins, J.O., & McMahan, R.. Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis. United States. doi:10.1016/0360-3016(85)90175-0.
Powell, B.L., Jackson, D.V. Jr., Scarantino, C.W., Pope, E., Choplin, R., Craig, J.B., Atkins, J.N., Cooper, M.R., Hopkins, J.O., and McMahan, R.. 1985. "Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis". United States. doi:10.1016/0360-3016(85)90175-0.
@article{osti_5548340,
title = {Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis},
author = {Powell, B.L. and Jackson, D.V. Jr. and Scarantino, C.W. and Pope, E. and Choplin, R. and Craig, J.B. and Atkins, J.N. and Cooper, M.R. and Hopkins, J.O. and McMahan, R.},
abstractNote = {Sequential hemibody irradiation (SHB) was integrated with combination chemotherapy and local irradiation (LRT) in the induction and consolidation phases of a therapeutic protocol for small cell lung carcinoma (SCLC). Forty-one previously untreated patients were entered into this program. Among 38 evaluable patients (20 with limited disease (LD) and 18 with extensive disease (ED)), the overall response rate was 63% (90% in LD and 33% in ED patients). The estimated overall survival is 8.1 months. The major toxicity has been myelosuppression - especially thrombocytopenia. The frequency of previously described acute radiation syndromes and radiation pneumonitis associated with hemibody irradiation have been substantially decreased at the current dosage with premedication and shielding techniques.},
doi = {10.1016/0360-3016(85)90175-0},
journal = {Int. J. Radiat. Oncol., Biol. Phys.; (United States)},
number = ,
volume = 11:3,
place = {United States},
year = 1985,
month = 3
}
  • Fourteen patients with small cell bronchogenic carcinoma, five with extensive disease and nine with localized disease, were treated with cyclophosphamide (1.5 g/m2 iv, Days 1 and 22), lomustine (70 mg/m2 orally, Day 1), and methotrexate (15 mg/m2 twice weekly during Weeks 2, 3, 5, and 6). UHBI (600 rads) was given during Week 6 in a single dose and LCI was given during Week 7 (2000 rads/five fractions) to the tumor and mediastinum. Maintenance chemotherapy began in Week 12 with cyclophosphamide (700 mg/m2 iv every 3 weeks) and lomustine (70 mg/m2 orally every 6 weeks). Twelve patients were evaluable formore » response and toxicity (eight with limited disease). There were three complete response and seven partial responses after induction chemotherapy. After completion of the consolidation radiation therapy, all 12 patients had a response: six complete responses and six partial responses. Acute toxic effects included nausea and vomiting in eight patients, fever in five, and hypotension and angina in one. Subacute toxic effects included nausea, vomiting, and dehydration in two patients who required hospitalization, prolonged aplasia in one, reversible radiation esophagitis in three. Three patients had radiation pneumonitis including one with bilateral diffuse disease that led to death from respiratory failure. Only two of 12 patients received their maintenance therapy on schedule. Treatment failures occurred within the LCI field in seven patients and in distant metastatic sites in six. The median time to first relapse was 7 months and the median survival was 9 months. Because of toxicity, treatment delays, and poor survival in this group of patients, we cannot recommend this combined modality approach.« less
  • Between October 1974 and December 1980, 123 patients with limited small cell carcinoma were treated in the Indiana University Medical Center Department of Radiation Oncology. Of these, 115 were treated with preplanned combined modality therapy using irradiation and polychemotherapy (Adriamycin, Cytoxan and Oncovin). All patients received whole brain prophylactic irradiation and were followed a minimum of 2 years. Sixty-six patients were given chest irradiation with all but two receiving 3500-4000 rad while 49 did not receive this treatment. Sixty-five percent of those patients receiving chest irradiation had a complete response to therapy, as opposed to 33% who did not. Thismore » study demonstrates an increase response rate, median survival, and overall survival in patients receiving chest irradiation. The high rate of relapse in the chest suggests the need for more effective control of the primary. This may be accomplished by increasing the dose of chest irradiation or surgical removal when feasible.« less
  • A total of 304 patients with limited small-cell carcinoma of the lung were treated with a combination of cyclophosphamide, Adriamycin, and vincristine (CAV) and elective brain irradiation (3,600 rad TD in 14 fractions). The patients were randomized to either receive or not receive thoracic irradiation (4000 rad TD, split course). Of the 304 patients, 291 were eligible for the study. Two hundred eighteen (75%) were completely evaluable. In each group, 81% of the patients had a Karnofsky index of 80% or higher and 14% had supraclavicular or scalene lymph nodes. Patients treated with CAV and no thoracic irradiation had amore » complete response (CR) of 48%, in contrast to 63% for those receiving chest irradiation. In the first group, the complete and partial response rate was 70%; in the second, 80%. The median survival for the eligible patients treated with CAV and brain radiation therapy was 49 weeks; for those treated with the same regimen plus thoracic irradiation, the median survival was 60 weeks. The actuarial two-year tumor-free survival is 19% in the first group and 28% in the second group. The median survival for the responders in the CAV plus brain irradiation group was 57 weeks and for those receiving thoracic irradiation, 78 weeks. Thoracic failure was 52% in patients not treated with thoracic radiation therapy v 36% in those receiving it (P . .06). The distant metastases incidence was 23% in patients not treated with thoracic radiation and 35% in patients treated with thoracic radiation. Hematologic toxicity was comparable in both groups; 30% of the patients had moderate to severe granulocytopenia and 6%, low homoglobin. Two toxicity-related deaths occurred (one in each group). Moderate gastrointestinal toxicity was noted in 41% and severe in 16% of the patients receiving CAV and brain irradiation without thoracic radiotherapy v 44% and 20% in those irradiated in the thorax.« less
  • A new combined radiation-chemotherapy protocol for the treatment of small cell lung carcinoma has produced unexpectedly severe normal tissue injury during radiation therapy. Thirteen of 23 patients who received radiation treatment plus combination chemotherapy (Vincristine, Adriamycin, Cyclophosphamide and VP16-213 (epipodophyllotoxin)) developed severe epithelial reactions from relatively low radiation doses. Prior experience with combination of radiation and chemotherapy leads us to implicate VP16-213 as the agent responsible for the enhanced radiation reactions.
  • The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0more » months (p > 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.« less