Combined alkylators and multiple-site irradiation for extensive small cell lung cancer: A Southwest Oncology Group study

Robert B Livingston, S. Schulman, J. G. Mira, G. Harker, S. Vogel, C. A. Coltman, S. E. Rivkin, G. T. Budd, M. R. Grever, J. P. Crowley

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The Southwest Oncology Group performed a study for patients with extensive small cell lung cancer in which two hypotheses were tested: (a) that combined alkylating agents for induction might improve the initial response rate; and (b) that multiple-site, involved-field consolidation with irradiation in patients with response to chemotherapy might further improve response quality and duration. A regimen of combined alkylating agents plus vincristine [carmustine, thiotepa, vincristine, and cyclophosphamide (BTOC)] was compared to our standard program of cyclophosphamide, doxorubicin, and vincristine (CAV). Patients with bone marrow metastases and/or disseminated bone metastases were randomized to BTOC or CAV as initial induction therapy, but received no multiple-field irradiation afterward. Among 189 such patients, the overall response rates were similar (48% to BTOC and 61% to CAV, with complete remission in 5% and 15%, respectively). Toxic effects were also comparable, with 23% sustaining life-threatening or fatal complications on BTOC and 16% on CAV. Median survival (5.9 and 7 months for BTOC and CAV, respectively) and overall survival were not different, and are superimposable upon our previously reported results with CAV alone. For patients with no evidence of bone marrow involvement and no metastases identified beyond the confines of ipsilateral hemithorax, liver, and brain, the plan of therapy consisted of induction chemotherapy (BTOC or CAV) every 3 weeks for three cycles, followed by multiple-field irradiation consolidation to sites of prior involvement. Among 239 such patients, response rates to therapy initiated with BTOC and CAV were also similar: 54% for BTOC and 62% for CAV, with complete response in 16% and 13%, respectively. However, the program of BTOC followed by multiple-site irradiation was associated with a higher incidence of severe or life-threatening thrombocytopenia (23% versus 8% for CAV), accounted for almost entirely by patients receiving hepatic irradiation after chemotherapy, among whom the incidence of this complication (grade 3 or 4) was 76% and 14%, respectively. Other toxic effects, including granulocytopenia were comparable. With the exception of thrombocytopenia in the cites subgroup, multiple-field irradiation consolidation proved feasible and tolerable, with improved quality of response evident after its initiation in 24% of 135 patients. However, a similar proportion developed disease progression during or shortly after radiation therapy, and the median survival of patients who received irradiation was only 9 months (7 months from the start of consolidation). Neither combined alkylating agents at doses equitoxic to CAV nor the use of multiple-site, involved-field irradiation as a consolidation measure can be recommended, based on the outcome of this study.

Original languageEnglish (US)
Pages (from-to)1395-1401
Number of pages7
JournalCancer Treatment Reports
Volume70
Issue number12
StatePublished - 1986
Externally publishedYes

Fingerprint

Alkylating Agents
Small Cell Lung Carcinoma
Vincristine
Cyclophosphamide
Doxorubicin
Poisons
Neoplasm Metastasis
Thrombocytopenia
Survival
Bone Marrow
Thiotepa
Drug Therapy
Carmustine
Agranulocytosis
Induction Chemotherapy
Liver
Incidence
Disease Progression
Radiotherapy
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Livingston, R. B., Schulman, S., Mira, J. G., Harker, G., Vogel, S., Coltman, C. A., ... Crowley, J. P. (1986). Combined alkylators and multiple-site irradiation for extensive small cell lung cancer: A Southwest Oncology Group study. Cancer Treatment Reports, 70(12), 1395-1401.

Combined alkylators and multiple-site irradiation for extensive small cell lung cancer : A Southwest Oncology Group study. / Livingston, Robert B; Schulman, S.; Mira, J. G.; Harker, G.; Vogel, S.; Coltman, C. A.; Rivkin, S. E.; Budd, G. T.; Grever, M. R.; Crowley, J. P.

In: Cancer Treatment Reports, Vol. 70, No. 12, 1986, p. 1395-1401.

Research output: Contribution to journalArticle

Livingston, RB, Schulman, S, Mira, JG, Harker, G, Vogel, S, Coltman, CA, Rivkin, SE, Budd, GT, Grever, MR & Crowley, JP 1986, 'Combined alkylators and multiple-site irradiation for extensive small cell lung cancer: A Southwest Oncology Group study', Cancer Treatment Reports, vol. 70, no. 12, pp. 1395-1401.
Livingston, Robert B ; Schulman, S. ; Mira, J. G. ; Harker, G. ; Vogel, S. ; Coltman, C. A. ; Rivkin, S. E. ; Budd, G. T. ; Grever, M. R. ; Crowley, J. P. / Combined alkylators and multiple-site irradiation for extensive small cell lung cancer : A Southwest Oncology Group study. In: Cancer Treatment Reports. 1986 ; Vol. 70, No. 12. pp. 1395-1401.
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abstract = "The Southwest Oncology Group performed a study for patients with extensive small cell lung cancer in which two hypotheses were tested: (a) that combined alkylating agents for induction might improve the initial response rate; and (b) that multiple-site, involved-field consolidation with irradiation in patients with response to chemotherapy might further improve response quality and duration. A regimen of combined alkylating agents plus vincristine [carmustine, thiotepa, vincristine, and cyclophosphamide (BTOC)] was compared to our standard program of cyclophosphamide, doxorubicin, and vincristine (CAV). Patients with bone marrow metastases and/or disseminated bone metastases were randomized to BTOC or CAV as initial induction therapy, but received no multiple-field irradiation afterward. Among 189 such patients, the overall response rates were similar (48{\%} to BTOC and 61{\%} to CAV, with complete remission in 5{\%} and 15{\%}, respectively). Toxic effects were also comparable, with 23{\%} sustaining life-threatening or fatal complications on BTOC and 16{\%} on CAV. Median survival (5.9 and 7 months for BTOC and CAV, respectively) and overall survival were not different, and are superimposable upon our previously reported results with CAV alone. For patients with no evidence of bone marrow involvement and no metastases identified beyond the confines of ipsilateral hemithorax, liver, and brain, the plan of therapy consisted of induction chemotherapy (BTOC or CAV) every 3 weeks for three cycles, followed by multiple-field irradiation consolidation to sites of prior involvement. Among 239 such patients, response rates to therapy initiated with BTOC and CAV were also similar: 54{\%} for BTOC and 62{\%} for CAV, with complete response in 16{\%} and 13{\%}, respectively. However, the program of BTOC followed by multiple-site irradiation was associated with a higher incidence of severe or life-threatening thrombocytopenia (23{\%} versus 8{\%} for CAV), accounted for almost entirely by patients receiving hepatic irradiation after chemotherapy, among whom the incidence of this complication (grade 3 or 4) was 76{\%} and 14{\%}, respectively. Other toxic effects, including granulocytopenia were comparable. With the exception of thrombocytopenia in the cites subgroup, multiple-field irradiation consolidation proved feasible and tolerable, with improved quality of response evident after its initiation in 24{\%} of 135 patients. However, a similar proportion developed disease progression during or shortly after radiation therapy, and the median survival of patients who received irradiation was only 9 months (7 months from the start of consolidation). Neither combined alkylating agents at doses equitoxic to CAV nor the use of multiple-site, involved-field irradiation as a consolidation measure can be recommended, based on the outcome of this study.",
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T1 - Combined alkylators and multiple-site irradiation for extensive small cell lung cancer

T2 - A Southwest Oncology Group study

AU - Livingston, Robert B

AU - Schulman, S.

AU - Mira, J. G.

AU - Harker, G.

AU - Vogel, S.

AU - Coltman, C. A.

AU - Rivkin, S. E.

AU - Budd, G. T.

AU - Grever, M. R.

AU - Crowley, J. P.

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N2 - The Southwest Oncology Group performed a study for patients with extensive small cell lung cancer in which two hypotheses were tested: (a) that combined alkylating agents for induction might improve the initial response rate; and (b) that multiple-site, involved-field consolidation with irradiation in patients with response to chemotherapy might further improve response quality and duration. A regimen of combined alkylating agents plus vincristine [carmustine, thiotepa, vincristine, and cyclophosphamide (BTOC)] was compared to our standard program of cyclophosphamide, doxorubicin, and vincristine (CAV). Patients with bone marrow metastases and/or disseminated bone metastases were randomized to BTOC or CAV as initial induction therapy, but received no multiple-field irradiation afterward. Among 189 such patients, the overall response rates were similar (48% to BTOC and 61% to CAV, with complete remission in 5% and 15%, respectively). Toxic effects were also comparable, with 23% sustaining life-threatening or fatal complications on BTOC and 16% on CAV. Median survival (5.9 and 7 months for BTOC and CAV, respectively) and overall survival were not different, and are superimposable upon our previously reported results with CAV alone. For patients with no evidence of bone marrow involvement and no metastases identified beyond the confines of ipsilateral hemithorax, liver, and brain, the plan of therapy consisted of induction chemotherapy (BTOC or CAV) every 3 weeks for three cycles, followed by multiple-field irradiation consolidation to sites of prior involvement. Among 239 such patients, response rates to therapy initiated with BTOC and CAV were also similar: 54% for BTOC and 62% for CAV, with complete response in 16% and 13%, respectively. However, the program of BTOC followed by multiple-site irradiation was associated with a higher incidence of severe or life-threatening thrombocytopenia (23% versus 8% for CAV), accounted for almost entirely by patients receiving hepatic irradiation after chemotherapy, among whom the incidence of this complication (grade 3 or 4) was 76% and 14%, respectively. Other toxic effects, including granulocytopenia were comparable. With the exception of thrombocytopenia in the cites subgroup, multiple-field irradiation consolidation proved feasible and tolerable, with improved quality of response evident after its initiation in 24% of 135 patients. However, a similar proportion developed disease progression during or shortly after radiation therapy, and the median survival of patients who received irradiation was only 9 months (7 months from the start of consolidation). Neither combined alkylating agents at doses equitoxic to CAV nor the use of multiple-site, involved-field irradiation as a consolidation measure can be recommended, based on the outcome of this study.

AB - The Southwest Oncology Group performed a study for patients with extensive small cell lung cancer in which two hypotheses were tested: (a) that combined alkylating agents for induction might improve the initial response rate; and (b) that multiple-site, involved-field consolidation with irradiation in patients with response to chemotherapy might further improve response quality and duration. A regimen of combined alkylating agents plus vincristine [carmustine, thiotepa, vincristine, and cyclophosphamide (BTOC)] was compared to our standard program of cyclophosphamide, doxorubicin, and vincristine (CAV). Patients with bone marrow metastases and/or disseminated bone metastases were randomized to BTOC or CAV as initial induction therapy, but received no multiple-field irradiation afterward. Among 189 such patients, the overall response rates were similar (48% to BTOC and 61% to CAV, with complete remission in 5% and 15%, respectively). Toxic effects were also comparable, with 23% sustaining life-threatening or fatal complications on BTOC and 16% on CAV. Median survival (5.9 and 7 months for BTOC and CAV, respectively) and overall survival were not different, and are superimposable upon our previously reported results with CAV alone. For patients with no evidence of bone marrow involvement and no metastases identified beyond the confines of ipsilateral hemithorax, liver, and brain, the plan of therapy consisted of induction chemotherapy (BTOC or CAV) every 3 weeks for three cycles, followed by multiple-field irradiation consolidation to sites of prior involvement. Among 239 such patients, response rates to therapy initiated with BTOC and CAV were also similar: 54% for BTOC and 62% for CAV, with complete response in 16% and 13%, respectively. However, the program of BTOC followed by multiple-site irradiation was associated with a higher incidence of severe or life-threatening thrombocytopenia (23% versus 8% for CAV), accounted for almost entirely by patients receiving hepatic irradiation after chemotherapy, among whom the incidence of this complication (grade 3 or 4) was 76% and 14%, respectively. Other toxic effects, including granulocytopenia were comparable. With the exception of thrombocytopenia in the cites subgroup, multiple-field irradiation consolidation proved feasible and tolerable, with improved quality of response evident after its initiation in 24% of 135 patients. However, a similar proportion developed disease progression during or shortly after radiation therapy, and the median survival of patients who received irradiation was only 9 months (7 months from the start of consolidation). Neither combined alkylating agents at doses equitoxic to CAV nor the use of multiple-site, involved-field irradiation as a consolidation measure can be recommended, based on the outcome of this study.

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