We conducted a prospective, randomized study to clarify the role of radiotherapy of the primary tumor in limited small-cell cancer of the lung. After stratification for sex and for performance score based on the ability to ambulate, patients were randomly assigned to receive initial radiotherapy plus chemotherapy, delayed radiotherapy plus chemotherapy, or chemotherapy alone. The chemotherapy consisted of cyclophosphamide, etoposide (VP-16-213), and vincristine, with doxorubicin subsequently replacing etoposide in alternate cycles 7 through 18. Chemotherapy was given every three weeks for 18 months. The radiotherapy comprised 4000 rad in four weeks, followed by a 1000-rad "boost" directed against residual disease. All patients received prophylactic whole-brain radiation. The patients enrolled totaled 426, and 399 were evaluable. There was a statistically significant difference in the frequency of complete responses in favor of the two radiotherapy regimens (P = 0.0013). Failure-free survival was also longer with these two regimens (P less than 0.001), as was the interval before treatment failure in the chest (P less than 0.001) and overall survival (P = 0.0099). As expected, toxic effects--chiefly neutropenia--were also increased. The addition of radiotherapy of the primary tumor to combination chemotherapy improved both complete-response rates and survival, with increased but acceptable toxicity.

Chemotherapy with or without Radiation Therapy in Limited Small-Cell Carcinoma of the Lung

Cancer and Leukemia Group B (CALGB) accrued 1,745 patients with limited (LD) or extensive (ED) small-cell lung cancer (SCCL) to five separate trials between 1972 and 1986. We reviewed these data to evaluate the impact of pretreatment prognostic factors on outcome. In multivariate analysis, female gender was predictive of improved response (LD, P = .01; ED, P = .04) and survival (LD, P = .01; ED, P = .02). A performance status of 0 or 1 was associated with improved response rates in both subsets, but was statistically significant (P = .04) only for overall objective response in LD patients. Performance status was a highly significant predictor of survival in both LD and ED groups (P less than .001). Supraclavicular lymph node involvement, while still LD, had a borderline unfavorable impact on survival (P = .06) compared with a lesser extent of LD involvement. In ED patients, a decrease in survival rates was associated with an increased number of metastatic sites (P = .01). Changes in the patient population...

Prognostic factors in small-cell carcinoma of the lung: an analysis of 1,521 patients.

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.

Socioeconomic status and cancer survival.

The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and...

A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B.

BACKGROUND

To determine the changes in clinical trials and outcomes of patients with limited-stage small cell lung carcinoma (SCLC) treated on Phase III randomized trials initiated in North America between 1972 and1992.



METHODS

Phase III trials from 1972 to 1992 for patients with limited-stage SCLC were identified. Patients with limited-stage SCLC treated during a similar time interval were also evaluated in the Surveillance, Epidemiology, and End Results (SEER) database. Trends were tested in the number of trials, in the number and gender of patients entered on trial, and in survival duration over time.



RESULTS

Thirty trials involving 6564 patients were eligible for analyses. Nineteen trials (61%) involving 3626 patients were initiated within the first half of this time period (1972–1981). The median of median survival times of all patients treated on the control arms of the Phase III trials initiated between 1972 and 1981 and between 1982 and 1992 were 12.0 months (range, 10–16 months) and 17.0 months (range, 11–20 months), respectively (P < 0.001). Of 26 studies available for survival analysis, 5 (19%) showed a statistically significant survival prolongation in the experimental arm compared with the control arm with a median prolongation of 3.4 months (range, 1–5.2 months). All five evaluated some aspect of thoracic radiation therapy. Over a similar time period, there was a 6.4-month increase in the median survival of limited-stage SCLC patients listed in the SEER database (P < 0.0001) and a more than doubling of the 5-year survival from 5.2% to 12.1% (P = 0.0001).



CONCLUSIONS

Analyses of the patients with limited-stage SCLC treated on Phase III trials in North America initiated between 1972 and 1992 and those listed in the SEER database show significant improvements in median survivals. Furthermore, the 5-year survival of patients with limited-stage SCLC listed in the SEER database has more than doubled over the last 25 years. Further research will be needed to determine the relative contribution of improved therapy, supportive care, and stage migration to this prolongation in survival. Cancer 2002;95:1528–38. © 2002 American Cancer Society.



DOI 10.1002/cncr.10841

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.10841

Twenty‐five years of clinical research for patients with limited‐stage small cell lung carcinoma in North America

Patients with limited-stage small-cell carcinoma of the lung (SCCL) were randomly assigned to a four-drug chemotherapy program consisting of methotrexate, doxorubicin, cyclophosphamide, and CCNU (MACC) or to a regimen consisting of cyclophosphamide, CCNU, and vincristine alternated with Adriamycin (Adria Laboratories, Columbus, Ohio) and vincristine (CCV/AV). All patients received 4,500 cGy, in a split course, to the primary tumor, mediastinum, and supraclavicular lymph node drainage areas and 3,000 cGy to the whole brain. After four cycles of chemotherapy, patients were randomly assigned to chemotherapy plus methanol extractable residue of BCG (MER-BCG) or no MER-BCG. The complete response frequencies were similar for the two regimens (54% and 48%) as were the median survivals (12.0 and 11.5 months) and the two-year survival rates (15% and 17%). Immunotherapy with MER-BCG did not prolong the time to disease progression or improve survival. Women had a greater chance of achieving a complete remission independent of performance status. There was a complex interaction between sex and the chemotherapy regimens that may have important implications for the design and stratification of future trials in SCCL.

Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III cancer and Leukemia Group B Study

P Chahinian

Papers

Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III cancer and Leukemia Group B Study