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Infusion cisplatin chemotherapy and hyperfractionated thoracic radiotherapy for small-cell lung cancer
Abstracts
396
/ Lung
Cancer
110: occur in patients with small cell lung cancer. The significance of these mutations in the development of resistance to etoposide needs further investigation.
Radiotherapy Three-dimensional conformal radiation therapy in bronchogenie carcinoma Emami B. Radiation Oncology Cente,: 1939 Chit&n b Place, St. Louis, A40 63110. Semin Radial Oncol 1996;6:92-7. Radiotherapy represents one of the primary modalities in the treatment of patients with carcinoma of the lung. Despite significant medical advancements, the outcome of therapy (local control and survival) in patients with unresectabledisease is still very disappointing. Although there are some indications in the literature to suggest that higher doses of radiation may result in improved local control, the proximity of critical normal structures to the primary tumor precludes delivery of curative doses without increased risk of unacceptable complications. Three-dimensional conformal radiation therapy has shown a significant potential for improving radiation treatment planning in several sites, both for tumor coverage and sparing normal tissue. Using this technology. significant improvement in uncomplicated locoregional control of lung cancer may be possible. The following is a review of literature and analysis of the currently available information on this subject. A palliative accelerated irradiation regimen (PAIR) for advanced non-small-cell lung cancer (NSCLC) Nestle U. Nieder C, Abel U, Niewald M, Ukena D, Be&rich W et al. Abteilung fur Strahlentherapie. 66121 Hombu@uar: Radiother
Radiologische
Universitatsklinik,
D-
Oncol 1996;38: 195-203. In order to avoid overtreatment in advanced NSCLC we developed a palliativeaccelemted irradiation regimen (PAIR) applying a total dose of 32 Gy in 10 days with two daily fractions of 2 Gy. This paper reports on a l-year pilot study carried out in preparation of a randomised trial. Data for the 34 patients receiving PAIR were compared to 179 conventionaliy irradiated historical controls selected from a preexisting database according to identical inclusion criteria. Statistical analysis showed that PAIR patients had a significantly longer survival than controls (P = 0.0029). Median survival was 11.8 and 5.8 months, respectively, while l-year survival was 45.6% vs. 2 1.2%. Compared to the subgroup of controls who had received the full planned dose of 60 Gy (n = 104) PAIR patients showed no significant difference in survival. In order lo adjust for possible imbalances we used a comprehensive blinded prognostic rating design creating one score value per patient out of several known prognostic factors. After adjustment for the resulting prognostic score by means of the Cox proportional hazards model PAIR patients still showed significantly longer survival. We conclude that in advanced NSCLC survival after a palliative short-term regimen appears lo be at least equivalent to that following conventional high-dose irradiation.
Combined treatment modalities Combined chemotherapy and radiation therapy in surgically unresectable regionally advanced non-small cell lung cancer Komaki R. Department of Radiotherapy, UTMD Anderson Cancer Center: Box 97, Houston, TX 77030. Semin Radiat Oncol 1996;6:8691.
IS (1996)
381-399
There have been increasing reports suggesting that combined treatment modality is superior to one modality approach in regard to median and 2-year survivals, and local control for patients with locally advanced unresectable (stage III) non-small cell lung cancer. However, there are five major issues to be discussed before the above conclusion will be drawn. First, the staging system for lung cancer is not perfect andextent of m&static workup iscontroversial for patients with locally advanced unresectable non-small cell lung cancer. It is diicult to compare studies which have not mentioned the proportion of stage IIIA to stage IIIB nor completeness of staging workup. The second controversiaI area is selection of patients to be treated by combined modality. Third, definition of unresectability changes depending on the surgeon’s aggressiveness, skills, experience, and back-up system, including other speciality groups and facilities as well as the patient’s modalities are still under investigation. Finally, rates of toxicity of the combined modality need to be reported as well as efficacy of treatment. Infusion cisplatin chemotherapy and hyperfractionated thoracic radiotherapy for small-cell lung cancer Frytak S, Shaw EG, Jett JR, Richardson RL. Foote RL, Creagan ET et al. Mayo Clinic, 200 First Street. Rocheste,: MN 55905. Am J Clin Oncol Cancer Clin Trials 1996;19:193-8. Sixty patients, 29 with limited disease and 31 with extensive disease, received an infusion cisplatin-based chemotherapy regimen and, where applicable, subsequent hyperfractionated thoracic radiation therapy (HTRT). Of the patients with limited disease, the response rate was 100% (76% complete response); median survival 26.5 months: Iand 2-year survival 90 and 55%, respectively. Of those with extensive disease, 96% responded (36%complete response) with median survival 12.0 months and I- and P-year survival 48 and 29%. respectively. Thirtyfive percent ofextensive disease patients were downstaged to a ‘limited’ status, with a median survival of 20.3 months. Grade IV leukopenia and thrombocytopenia were seen in 25 and 7% ofpatients. respectively, with one patient dying of radiation pneumonitis. Within the constraints of the study, infusion cisplatin-based chemotherapy and HTRT appear to be a safe and effective program for the treatment of small-cell lung cancer. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-smallcell lung cancer: A randomized study Jeremic B, Shibamoto Y, Acimotic L, Milisavljevic S. Department of Oncology,
606-01.
Chest Disease
Research
Institute.
Kyoto
Universily.
Kyoto
J Clin Oncol 1996;14:1065-70. Purpose: To investigate the efficacy of concurrent hyperfractionated radiation therapy (HFX RT) and low-dose daily chemotherapy (CHT) in stage III non-small-cell lung cancer (NSCLC). Patients andMethods: Between January 1990 and December 199 1I I3 1 patients with histologically or cytologically confirmed stage III NSCLC, Kamofsky performance status (KPS) 50, and no previous therapy were randomly treated as follows: group I, HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy (n = 66); and group II, same HFX RT with CHT consisting of 50 mg of carboplatin (CBDCA) and 50 mg of etoposide (VP-16) given on each RT day (n = 65). Results: Group II patients had a significantly longer survival time than group I patients, with a median survival of 22 versus 14 months and 4-year survival rates of 23% versus 9% (P = .02 I). The median time to local recurrence and 4-year local recurrence- free survival rate were also significantly higher in group II than in group I (25 v 20 months and 42% v 19%. respectively. P = ,015). In contrast, the distant metastasis-free survival
396
/ Lung
Cancer
110: occur in patients with small cell lung cancer. The significance of these mutations in the development of resistance to etoposide needs further investigation.
Radiotherapy Three-dimensional conformal radiation therapy in bronchogenie carcinoma Emami B. Radiation Oncology Cente,: 1939 Chit&n b Place, St. Louis, A40 63110. Semin Radial Oncol 1996;6:92-7. Radiotherapy represents one of the primary modalities in the treatment of patients with carcinoma of the lung. Despite significant medical advancements, the outcome of therapy (local control and survival) in patients with unresectabledisease is still very disappointing. Although there are some indications in the literature to suggest that higher doses of radiation may result in improved local control, the proximity of critical normal structures to the primary tumor precludes delivery of curative doses without increased risk of unacceptable complications. Three-dimensional conformal radiation therapy has shown a significant potential for improving radiation treatment planning in several sites, both for tumor coverage and sparing normal tissue. Using this technology. significant improvement in uncomplicated locoregional control of lung cancer may be possible. The following is a review of literature and analysis of the currently available information on this subject. A palliative accelerated irradiation regimen (PAIR) for advanced non-small-cell lung cancer (NSCLC) Nestle U. Nieder C, Abel U, Niewald M, Ukena D, Be&rich W et al. Abteilung fur Strahlentherapie. 66121 Hombu@uar: Radiother
Radiologische
Universitatsklinik,
D-
Oncol 1996;38: 195-203. In order to avoid overtreatment in advanced NSCLC we developed a palliativeaccelemted irradiation regimen (PAIR) applying a total dose of 32 Gy in 10 days with two daily fractions of 2 Gy. This paper reports on a l-year pilot study carried out in preparation of a randomised trial. Data for the 34 patients receiving PAIR were compared to 179 conventionaliy irradiated historical controls selected from a preexisting database according to identical inclusion criteria. Statistical analysis showed that PAIR patients had a significantly longer survival than controls (P = 0.0029). Median survival was 11.8 and 5.8 months, respectively, while l-year survival was 45.6% vs. 2 1.2%. Compared to the subgroup of controls who had received the full planned dose of 60 Gy (n = 104) PAIR patients showed no significant difference in survival. In order lo adjust for possible imbalances we used a comprehensive blinded prognostic rating design creating one score value per patient out of several known prognostic factors. After adjustment for the resulting prognostic score by means of the Cox proportional hazards model PAIR patients still showed significantly longer survival. We conclude that in advanced NSCLC survival after a palliative short-term regimen appears lo be at least equivalent to that following conventional high-dose irradiation.
Combined treatment modalities Combined chemotherapy and radiation therapy in surgically unresectable regionally advanced non-small cell lung cancer Komaki R. Department of Radiotherapy, UTMD Anderson Cancer Center: Box 97, Houston, TX 77030. Semin Radiat Oncol 1996;6:8691.
IS (1996)
381-399
There have been increasing reports suggesting that combined treatment modality is superior to one modality approach in regard to median and 2-year survivals, and local control for patients with locally advanced unresectable (stage III) non-small cell lung cancer. However, there are five major issues to be discussed before the above conclusion will be drawn. First, the staging system for lung cancer is not perfect andextent of m&static workup iscontroversial for patients with locally advanced unresectable non-small cell lung cancer. It is diicult to compare studies which have not mentioned the proportion of stage IIIA to stage IIIB nor completeness of staging workup. The second controversiaI area is selection of patients to be treated by combined modality. Third, definition of unresectability changes depending on the surgeon’s aggressiveness, skills, experience, and back-up system, including other speciality groups and facilities as well as the patient’s modalities are still under investigation. Finally, rates of toxicity of the combined modality need to be reported as well as efficacy of treatment. Infusion cisplatin chemotherapy and hyperfractionated thoracic radiotherapy for small-cell lung cancer Frytak S, Shaw EG, Jett JR, Richardson RL. Foote RL, Creagan ET et al. Mayo Clinic, 200 First Street. Rocheste,: MN 55905. Am J Clin Oncol Cancer Clin Trials 1996;19:193-8. Sixty patients, 29 with limited disease and 31 with extensive disease, received an infusion cisplatin-based chemotherapy regimen and, where applicable, subsequent hyperfractionated thoracic radiation therapy (HTRT). Of the patients with limited disease, the response rate was 100% (76% complete response); median survival 26.5 months: Iand 2-year survival 90 and 55%, respectively. Of those with extensive disease, 96% responded (36%complete response) with median survival 12.0 months and I- and P-year survival 48 and 29%. respectively. Thirtyfive percent ofextensive disease patients were downstaged to a ‘limited’ status, with a median survival of 20.3 months. Grade IV leukopenia and thrombocytopenia were seen in 25 and 7% ofpatients. respectively, with one patient dying of radiation pneumonitis. Within the constraints of the study, infusion cisplatin-based chemotherapy and HTRT appear to be a safe and effective program for the treatment of small-cell lung cancer. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-smallcell lung cancer: A randomized study Jeremic B, Shibamoto Y, Acimotic L, Milisavljevic S. Department of Oncology,
606-01.
Chest Disease
Research
Institute.
Kyoto
Universily.
Kyoto
J Clin Oncol 1996;14:1065-70. Purpose: To investigate the efficacy of concurrent hyperfractionated radiation therapy (HFX RT) and low-dose daily chemotherapy (CHT) in stage III non-small-cell lung cancer (NSCLC). Patients andMethods: Between January 1990 and December 199 1I I3 1 patients with histologically or cytologically confirmed stage III NSCLC, Kamofsky performance status (KPS) 50, and no previous therapy were randomly treated as follows: group I, HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy (n = 66); and group II, same HFX RT with CHT consisting of 50 mg of carboplatin (CBDCA) and 50 mg of etoposide (VP-16) given on each RT day (n = 65). Results: Group II patients had a significantly longer survival time than group I patients, with a median survival of 22 versus 14 months and 4-year survival rates of 23% versus 9% (P = .02 I). The median time to local recurrence and 4-year local recurrence- free survival rate were also significantly higher in group II than in group I (25 v 20 months and 42% v 19%. respectively. P = ,015). In contrast, the distant metastasis-free survival