2
279 There was a minimum 2-year follow-up. Local control was obtained in 8 of 26 evaluable patients (31%) treated with preoperative ra- diation therapy and surgery, 2 of 6 patients treated with radiation therapy alone, and 0 of 2 patients treated with surgery and postoperative radiation therapy. Twelve (30%) of 40 patients receiving planned pre- operative radiation therapy did not undergo definitive surgery. Absolute survival free of disease at 5 years by treatment group for patients at risk was 3 of 30 (10%) with preoperative radiation therapy and surgery, 0 of 3 with surgery and postoperative radi- ation therapy, and 2 of 7 with radiation therapy alone. Since one third of the pati- ents who received low- to moderate-dose preoperative radiation therapy did not undergo definitive surgery, and since there is a small but significant survival with radiation therapy alone, it seems unwise to give moderate-dose preoperative radiation therapy, which implies an unfavourable radi- ation technique for the unresectable cases. The recommendation is to treat patients with lesions believed to be resectable by initial surgery resection followed by high- dose radiation therapy in selected patients with questionable margins or positive lymph nodes. Those patients with borderline or apparently unresectable lesions are recom- mended to be treated with radiation therapy alone. Increased Survival with High-Dose Multifield Radiotherapy and Intensive Chemotherapy in Limited Small Cell Carcinoma of the Lung. Shank, B., Scher, H., Bilaris, BoS. et al. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, U.S.A. Cancer 56: 2771-2778, 1985. From June 1979 through April 1982, we treated 35 patients with limited cell car- cinoma on an intensive chemo-radio-immuno- therapy regimen, consisting of induction with cyclophosphamide, doxorubicin, and vincristine, alternately cycled with VP-16 and cisplatin. Patients were stratified by performance status an randomized to thymosin, fraction V, or no thymosin. Induction was followed by consolidation, consisting of prophylactic whole-brain radiotherapy and multified radiotherapy to the primary and mediastinum with cyclophosphamide and vin- cristine. Patients who were complete respon- ders (CRs) postconsolidation resumed mainte- nance immediately. Patients were followed from 1 to 3.8 years (median, 2.2 years) at the time of analysis. After induction, 35% (12/34) had become CRs; after conso- lidation radiotherapy, an additional 10/34 became CRs for a total CR rate of 65% (22/34). There were only 9/34 local failures (26%), of which all but one were inpatients who had not become CRs. A prolonged median sur- vival (21 months) has been obtained in pa- tients with limited small cell carcinoma of lung treated with an intensive combined modality regime n. At 1 year, survival is 83%; at 2 years, 46%. There is a 33% long- term survival (>3 years). There is no dif- ference in survival or recurrence rate be- tween patients treated with or without thy- mosin. Alternating Chemotherapy, Prophylactic Cra- nial Irradiation and Late Local Thoracic Irradiation for Small-Cell Lung Cancer. Ten Velde, G.P.M., Wouters, E.F.M., Greve, L.H. et al. Department of Pulmonelogy, St. Anadal Hospital, 6201 BX Maastricht, Nether- lands. Respiration 49: 216-221, 1986. 28 consecutive patients with small-cell lung cancer (SCLC) aged 48-78 years (with exclusion of 4 patients over 80 years) were treated with combination chemotherapy in the schedule AAA-BBB-AAA-BBB, wher~ A consisted of cycl~phosphamide 1,000 mg/m-~ adriamycin 50 mg/m, and etoposide i00 mg/~ ~ x 3 and B of cyclopho~phamide 1,000 mg/m , me~hotrex- ate 59 mg/m" and vincristine 1 mg/m ~ x 2. Patients in complete remission after 3 courses received prophylactic cranial irra- diation, and thoracic irradiation was given after completion of chemotherapy. There were 3 toxic deaths. Of the patients with limi- ted disease, 71% reached complete remission and 24% partial remission; in extensive dis- ease these percentages were 36 and 45%, re- spectively. Three patients survived more than 2 years, 1 with recurrence of squemous cell carcinoma after 125 weeks. It is concluded that this scheme of combination chemotherapy is as effective as those reported earlier in remission rate and survival in SCLC. However, the addition of thoracic irradia- tion failed to prevent local relapse in 83% of the patients. Three Months Treatment with Chemotherapy and-Radiotherapy for Small Cell Lung Cancer. Thatcher, N., Stout, R., Smith, D.B. et al. Cancer Research Campaign Department of Me- dical Oncology, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, U.K. Br. J, Cancer 52: 327-332, 1985. Fifty-five patients with inoperable but limited stage small cell carcinoma of the bronchus and a further 15 patients with contralateral neck nodes, pleural effusions and marrow involvement were entered into the study and treated. The 3 month treatment regimen comprised 3 courses of e~oposide with cyclophosphamide at 2.5 g/m fol- lowed by methotrexate and radiotherapy, no maintenance treatment was given. The com- plete response rate in the total patient group was 54% and the partial response rate 21%. The median survival was ii months for the 70 patients, 15 months for the complete

Three months treatment with chemotherapy and radiotherapy for small cell lung cancer

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Page 1: Three months treatment with chemotherapy and radiotherapy for small cell lung cancer

279

There was a minimum 2-year follow-up. Local control was obtained in 8 of 26 evaluable patients (31%) treated with preoperative ra- diation therapy and surgery, 2 of 6 patients treated with radiation therapy alone, and 0 of 2 patients treated with surgery and postoperative radiation therapy. Twelve (30%) of 40 patients receiving planned pre- operative radiation therapy did not undergo definitive surgery. Absolute survival free of disease at 5 years by treatment group for patients at risk was 3 of 30 (10%) with preoperative radiation therapy and surgery, 0 of 3 with surgery and postoperative radi- ation therapy, and 2 of 7 with radiation therapy alone. Since one third of the pati- ents who received low- to moderate-dose preoperative radiation therapy did not undergo definitive surgery, and since there is a small but significant survival with radiation therapy alone, it seems unwise to give moderate-dose preoperative radiation therapy, which implies an unfavourable radi- ation technique for the unresectable cases. The recommendation is to treat patients with lesions believed to be resectable by initial surgery resection followed by high- dose radiation therapy in selected patients with questionable margins or positive lymph nodes. Those patients with borderline or apparently unresectable lesions are recom- mended to be treated with radiation therapy alone.

Increased Survival with High-Dose Multifield Radiotherapy and Intensive Chemotherapy in Limited Small Cell Carcinoma of the Lung. Shank, B., Scher, H., Bilaris, BoS. et al. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, U.S.A. Cancer 56: 2771-2778, 1985.

From June 1979 through April 1982, we treated 35 patients with limited cell car- cinoma on an intensive chemo-radio-immuno- therapy regimen, consisting of induction with cyclophosphamide, doxorubicin, and vincristine, alternately cycled with VP-16 and cisplatin. Patients were stratified by performance status an randomized to thymosin, fraction V, or no thymosin. Induction was followed by consolidation, consisting of prophylactic whole-brain radiotherapy and multified radiotherapy to the primary and mediastinum with cyclophosphamide and vin- cristine. Patients who were complete respon- ders (CRs) postconsolidation resumed mainte- nance immediately. Patients were followed from 1 to 3.8 years (median, 2.2 years) at the time of analysis. After induction, 35% (12/34) had become CRs; after conso- lidation radiotherapy, an additional 10/34 became CRs for a total CR rate of 65% (22/34). There were only 9/34 local failures (26%), of which all but one were inpatients who

had not become CRs. A prolonged median sur-

vival (21 months) has been obtained in pa- tients with limited small cell carcinoma of lung treated with an intensive combined modality regime n. At 1 year, survival is 83%; at 2 years, 46%. There is a 33% long- term survival (>3 years). There is no dif- ference in survival or recurrence rate be- tween patients treated with or without thy- mosin.

Alternating Chemotherapy, Prophylactic Cra- nial Irradiation and Late Local Thoracic Irradiation for Small-Cell Lung Cancer. Ten Velde, G.P.M., Wouters, E.F.M., Greve, L.H. et al. Department of Pulmonelogy, St. Anadal Hospital, 6201 BX Maastricht, Nether- lands. Respiration 49: 216-221, 1986.

28 consecutive patients with small-cell lung cancer (SCLC) aged 48-78 years (with exclusion of 4 patients over 80 years) were treated with combination chemotherapy in the schedule AAA-BBB-AAA-BBB, wher~ A consisted of cycl~phosphamide 1,000 mg/m-~ adriamycin 50 mg/m, and etoposide i00 mg/~ ~ x 3 and B of cyclopho~phamide 1,000 mg/m , me~hotrex- ate 59 mg/m" and vincristine 1 mg/m ~ x 2. Patients in complete remission after 3 courses received prophylactic cranial irra- diation, and thoracic irradiation was given after completion of chemotherapy. There were 3 toxic deaths. Of the patients with limi- ted disease, 71% reached complete remission and 24% partial remission; in extensive dis- ease these percentages were 36 and 45%, re- spectively. Three patients survived more than 2 years, 1 with recurrence of squemous cell carcinoma after 125 weeks. It is concluded that this scheme of combination chemotherapy is as effective as those reported earlier in remission rate and survival in SCLC. However, the addition of thoracic irradia- tion failed to prevent local relapse in 83% of the patients.

Three Months Treatment with Chemotherapy and-Radiotherapy for Small Cell Lung Cancer. Thatcher, N., Stout, R., Smith, D.B. et al. Cancer Research Campaign Department of Me- dical Oncology, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, U.K. Br. J, Cancer 52: 327-332, 1985.

Fifty-five patients with inoperable but limited stage small cell carcinoma of the bronchus and a further 15 patients with contralateral neck nodes, pleural effusions and marrow involvement were entered into the study and treated. The 3 month treatment regimen comprised 3 courses of e~oposide with cyclophosphamide at 2.5 g/m fol- lowed by methotrexate and radiotherapy, no maintenance treatment was given. The com- plete response rate in the total patient group was 54% and the partial response rate 21%. The median survival was ii months for

the 70 patients, 15 months for the complete

Page 2: Three months treatment with chemotherapy and radiotherapy for small cell lung cancer

280

£esponders, and those patients with a bron~

choscopically confirmed complete response survived significantly longer. There was no significant difference between the pati- ents with strictly limited stage disease and those in the broader category. Eight patients are tumor free and alive one year or more after the end of treatment. The me- dian followup is 17 months. Twenty-four pa- tients were delayed 1-2 weeks during treat- ment because of chemotherapy induced toxici- ty. Six patients died probably of infection associated with leucopaenia. The majority of the patients' Karnofsky performance improved with the treatment as did their breathless- ness assessed on a respiratory score. The short intensive chemotherapy regimen of 3 months produced similar results to those following more prolonged treatment regimens.

A Randomized Comparison of the Effects of Adjuvant Therapy on Resected Stages II and III Non-Small Cell Carcinoma of the Lung. Holmes, E.C., Hill, L.D., Gail, M. UCLA, Los Angeles, CA, U.S.A.

The Lung Cancer Study Group has evalua- ted postoperative chemotherapy and immuno- therapy in patients with Stages II and III adenocarcinoma and large cell undifferentia- ted carcinoma. Patients were randomized following surgery and careful intraoperative staging to receive either chemotherapy or immunotherapy. Chemotherapy consisted of Cis Platinum (Reg. trademark), Adriamycin (Reg. trademark), and Cytoxan (Reg. trademark) and immunotherapy consisted of Levamisole (Reg. trademark) and Intrapleural BCG (Reg. trademark). Sixty-eight patients were rando- mized to the immunotherapy arm and 62 to the chemotherapy arm. There were 49 recurrences in the immunotherapy group and 35 in the chemotherapy group (p = 0.003). These studies indicate that surgical adjuvant chemotherapy is effective in prolonging the disease-free survival in patients with Stages II and III adenocarcinoma and large cell undifferentia- ted carcinoma. Patients with Stages II and III resected squamous cell carcinoma were randomized to receive postoperative radia- tion therapy or no further treatment. There was no significant difference in terms of survival between the two treatment groups. However, those who received radiation therapy had a significantly lower incidence of local recurrence (p = 0.001). These studies indi- cate that postoperative radiation therapy is effective in controlling the local disea- se but that effective systemic therapy is ne- cessary for improved survival in patients with Stages II and III squamous cell carci- noma of the lung.

Chemotherapy Pollowedby Lung Resection in Inoperable Non-Small Cell Lung Carcinomas Due to Locally Far-Advanced Disease.

Takita, H., Regal, A.-M., Antkowiak, J.G. et al. Department of Thoracic Surgery and Oncology, Roswell Park Memorial Institute, Buffalo, NY 14263, U.S.A. Cancer 57: 630- 635, 1986.

From 1977, 29 patients with inoperable non-small cell lung carcinoma due to local- ly far-advanced disease underwent lung re- section after receiving two to eight courses of chemotherapy. After the surgery was per- formed, three additional courses of chemo- therapy were given. The overall median sur- vival from onset of the chemotherapy was 30.5 months; postoperatively, it was 24.5 months (five patients survived > 5 years). Postoperative mortality was 10.3%. The over- all survival results compare favorably with those obtained with radiation therapy.

~0nsurgical Combined Modality Therapies in Non-Small Cell Lung Cancer. Klastersky, J., Sculier, J.P. Service de Medecine, Institut Jules Bordet, Centre des Tumeurs de l'Universite Libre de Bruxelles, Brussels, U.S.A. Chest 89: 289S-294S, 1986.

Nonsurgical combined approaches of non- small cell lung cancer represent a concept that has only been investigated so far with chemotherapy and radiation therapy. Thoracic irradiation of locoregional disease is asso- ciated with a high rate of local control and a 5-10% long-term (5-year) survival; however, distant metastases remain the main cause of failure. This observation suggests that the tumor is' often microscopically disseminated at the time of diagnosis. Systemic therapy therefore must be associated to radiation therapy to try to control both the undetec- table metastases and the local disease. How- ever, the results reported so far have been disappointing, probably because of the mo- dest activity of the available chemotherapy. Further progress with the combined approach requires new developments in the chemothe- rapy of non-small cell lung cancer, particu- larly the introduction of new active drugs.

The effect of Surgery, Radiation Therapy, and Combined Radiation Therapy and Chemo- therapy on Immunocompetence in Patients with Lung Carcinoma. Jakobsson, M., Taskinen, P.J., Ryhanen, P. et al. Department of Radiation Therapy, Oulu University Central Hospital, Oulu, Finland. Acta. Radiol., Ser. Oncol. 24: 481- 486, 1985.

The immunologic status of 59 patients with lung carcinoma was determined by ana- lysis of peripheral venous blood samples. The following tests were performed: total leucocyte and lymphocyte counts, the number of acid alpha-naphthyl acetate esterase (ANAE) positive cells (T-cells), and phyto- haemagglutinin (PHA) and tuberculin (PPD)

transformation tests. The patients were di-