Cancer Investigation, 10(2), 185-186 (1992)
Cancer Invest Downloaded from informahealthcare.com by McMaster University on 11/28/14 For personal use only.
Intensive Chemotherapy for ExtensiveStage Small-Cell Lung Cancer (SCLC) David Osoba, M.D. Division of Community Oncdogy British Columbia Cancer Agency and Department of Medicine University of British Columbia Columbia, Vancouver, Canada
After a major improvementin the treatment of SCLC during the late 1970s and the early 1980s, there has been a hiatus in progress until recent developments related to the early use of thoracic radiation (1) and intensive, weekly chemotherapy (2-4). An example of the latter in extensive-stage disease is the study reported by Wampler et al. in this issue. Although they treated only 14patients there is a suggestion of a high response rate which might translate into an improvement in survival. However, there were 3 deaths from sepsis and sepsis was present in an additional 6 patients. Neither prophylactic antibiotics nor granulocyte colony-stimulating factor (GCSF) were used in this study. It is important, therefore, to point out some important guidelines that should be followed in such protocols. The trials of intensive, weekly chemotherapy for extensive-stage SCLC were spurred, in part, by the success of similar therapy for lymphomas (5). In the latter, daily antibiotic prophylaxis using cotrimoxazole and ketoconazole was found to be successful in preventing sepsis. In addition, daily prednisone was effective in reducing the degree of granulocytopenia that might otherwise have been experienced. This supportive regimen was adopted in the protocol of cisplatin (C), vincristine (0), doxorubicin (D), and etoposide (E) used in 48 patients with extensive-stage SCLC at the Vancouver Clinic of the
British Columbia Cancer Agency (2). The overall incidence of sepsis was 8% with a further 8% developing herpetic infection, and there was only one neutropenic death (2%). In a parallel trial of CODE in patients with advanced non-small-cell lung cancer a small group of patients was treated without prednisone (6). Granulocytopenia was significantly more profound and was a reason for omitting or delaying chemotherapy significantlymore often than it was in patients who did receive prednisone. The use of G-CSF, or similar molecules, may indeed allow this kind of chemotherapy to be delivered safely (3), but it is still uncertain to what extent there may be an improvement in survival, and how expensive such a supportive regimen might be when compared to the less expensive regimen used at the B.C. Cancer Agency. Nevertheless, the potential benefits from intensive weekly chemotherapy for extensive-stagedisease represent a major advance in the chemotherapy of SCLC. In the B.C. Cancer Agency study, median survival was 61 weeks. Although this result cannot be compared directly to the results of other studies in extensive-stage disease because of differences in the patient poplations studied, this length of survival may be in the order of 20 weeks longer than that achievable by “standard” regimens. Stated another way, this may represent an increase in survival of about 50%. Should this magnitude of increase 185
Osoba
186
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in survival be confirmed and should it translate into a similar increase when similar regimens an:used in limitedstage disease, we then would expect to see median survivals in the order of 30 months and 4-yearsurvivals of 35 to 50%,particularly if thoracic radiation is given early in the course of treatment. If this turns out to be the case, a truly significant advance will have been achieved with relatively brief treatment regimens lasting 10-12 weeks and delivered entirely in the outpatient setting. While these numbers are clearly speculative at this time they provide, tlevertheless, a target to aim for in the therapy of SCLC.
REFERENCES 1. Murray N, Coy P, Pater Jet al: The importancsoftiming for thoracic irradiation (TI) in the canbined modality treament of limited stage
small cell lung cancer (LSCLC) (abstr). Proc Am SOCClin Oncol 10243, 1991. 2. Murray N, Shah A, Osoba D et al: Iltensive weekly chemotherapy for the treatmert of extensive stage mall cell lung cancer. J Clin 0 x 0 1 9: 1672, 1991. 3. Miles D, Harper P, Earl H et al: Inensive weekly chemotherapy
for good prognosis patients with small cell lung cancer (SCLC) (abstr). Proc Am Soc Clin Oncol 8225, 1989. 4. Masuda M, F h k a M, Negora N etal: CODE chemotherapy with or without recombinant hunan granulocytecobny-stimulatingfactor (rh G-CSF) in extensive-stage (ES) small cell lung cancer (SCLC) (abstr). Proc Am SOCClin Oncol 10:254, 1991. 5 . Klimo P, Connors JM: MACOP-B chemothetapy for the treatment of diffuse large-cell lymphoma. Ann Int Med 102:596-602, 1985. 6. Munay N, Osoba D, Shah A et al: Brid Intensive chemotherapy for metastatic nm-small-cell lung carcer: a phase II study of the weekly CODE regimen. J Natl Cancer Inst 83:190-194, 1991.
Cancer Invest Downloaded from informahealthcare.com by McMaster University on 11/28/14 For personal use only.
Intensive Chemotherapy for ExtensiveStage Small-Cell Lung Cancer (SCLC) David Osoba, M.D. Division of Community Oncdogy British Columbia Cancer Agency and Department of Medicine University of British Columbia Columbia, Vancouver, Canada
After a major improvementin the treatment of SCLC during the late 1970s and the early 1980s, there has been a hiatus in progress until recent developments related to the early use of thoracic radiation (1) and intensive, weekly chemotherapy (2-4). An example of the latter in extensive-stage disease is the study reported by Wampler et al. in this issue. Although they treated only 14patients there is a suggestion of a high response rate which might translate into an improvement in survival. However, there were 3 deaths from sepsis and sepsis was present in an additional 6 patients. Neither prophylactic antibiotics nor granulocyte colony-stimulating factor (GCSF) were used in this study. It is important, therefore, to point out some important guidelines that should be followed in such protocols. The trials of intensive, weekly chemotherapy for extensive-stage SCLC were spurred, in part, by the success of similar therapy for lymphomas (5). In the latter, daily antibiotic prophylaxis using cotrimoxazole and ketoconazole was found to be successful in preventing sepsis. In addition, daily prednisone was effective in reducing the degree of granulocytopenia that might otherwise have been experienced. This supportive regimen was adopted in the protocol of cisplatin (C), vincristine (0), doxorubicin (D), and etoposide (E) used in 48 patients with extensive-stage SCLC at the Vancouver Clinic of the
British Columbia Cancer Agency (2). The overall incidence of sepsis was 8% with a further 8% developing herpetic infection, and there was only one neutropenic death (2%). In a parallel trial of CODE in patients with advanced non-small-cell lung cancer a small group of patients was treated without prednisone (6). Granulocytopenia was significantly more profound and was a reason for omitting or delaying chemotherapy significantlymore often than it was in patients who did receive prednisone. The use of G-CSF, or similar molecules, may indeed allow this kind of chemotherapy to be delivered safely (3), but it is still uncertain to what extent there may be an improvement in survival, and how expensive such a supportive regimen might be when compared to the less expensive regimen used at the B.C. Cancer Agency. Nevertheless, the potential benefits from intensive weekly chemotherapy for extensive-stagedisease represent a major advance in the chemotherapy of SCLC. In the B.C. Cancer Agency study, median survival was 61 weeks. Although this result cannot be compared directly to the results of other studies in extensive-stage disease because of differences in the patient poplations studied, this length of survival may be in the order of 20 weeks longer than that achievable by “standard” regimens. Stated another way, this may represent an increase in survival of about 50%. Should this magnitude of increase 185
Osoba
186
Cancer Invest Downloaded from informahealthcare.com by McMaster University on 11/28/14 For personal use only.
in survival be confirmed and should it translate into a similar increase when similar regimens an:used in limitedstage disease, we then would expect to see median survivals in the order of 30 months and 4-yearsurvivals of 35 to 50%,particularly if thoracic radiation is given early in the course of treatment. If this turns out to be the case, a truly significant advance will have been achieved with relatively brief treatment regimens lasting 10-12 weeks and delivered entirely in the outpatient setting. While these numbers are clearly speculative at this time they provide, tlevertheless, a target to aim for in the therapy of SCLC.
REFERENCES 1. Murray N, Coy P, Pater Jet al: The importancsoftiming for thoracic irradiation (TI) in the canbined modality treament of limited stage
small cell lung cancer (LSCLC) (abstr). Proc Am SOCClin Oncol 10243, 1991. 2. Murray N, Shah A, Osoba D et al: Iltensive weekly chemotherapy for the treatmert of extensive stage mall cell lung cancer. J Clin 0 x 0 1 9: 1672, 1991. 3. Miles D, Harper P, Earl H et al: Inensive weekly chemotherapy
for good prognosis patients with small cell lung cancer (SCLC) (abstr). Proc Am Soc Clin Oncol 8225, 1989. 4. Masuda M, F h k a M, Negora N etal: CODE chemotherapy with or without recombinant hunan granulocytecobny-stimulatingfactor (rh G-CSF) in extensive-stage (ES) small cell lung cancer (SCLC) (abstr). Proc Am SOCClin Oncol 10:254, 1991. 5 . Klimo P, Connors JM: MACOP-B chemothetapy for the treatment of diffuse large-cell lymphoma. Ann Int Med 102:596-602, 1985. 6. Munay N, Osoba D, Shah A et al: Brid Intensive chemotherapy for metastatic nm-small-cell lung carcer: a phase II study of the weekly CODE regimen. J Natl Cancer Inst 83:190-194, 1991.
