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Nonoperative management of non-small cell lung cancer: The current Cancer and Leukemia Group B experience
158
Abstracts/Lung
Cancer
Multimudality therapy for non-small-cell lung cancer Lilenbaum RC, Green MR UCSD Cancer Centec 200 W&Arbor Drive, Sun Diego, CA 92103-8421. Oncology (USA) 1994;8:25-3 1. The optimal treatment strategy for patients with locally advanced (stage III) non-smallcell lung cancer remains controversial. Primary surgical resection 01 conventional thomcic irradiation alone results in poor longterm survival for the majority of stage III patients. Several multimodality strategies are reviewed in this article. Radiation followed by surgety may increase resectability, but its effects on smvivaJ are unproven. Sequential chemothempy and radiation have demonstrated a survival advantage for selected stage III patients. Chemotherapy followed by surgery has ah shown encouraging results, and additional studies are in progress. Concurrent chemoradiotherapy has shown conllicting results in a few randomized studies. Concurrent chemotherapy and radiation followed by surgery has been tested only in phase II trials and awaits further studies.
Surgery after radiochemotberapy for stage III lung cancer: Postoperative complications and late results Tavecchio L, Ravasi G, Bedini AV, Gramagha A, Milani F. Divisione OCT. lstituto Nazionole Tumori, Ma G Venezion I. 20133Milan. J Surg OncoI 1994;56:2-6. Fifty-seven stage III lung cancer patients underwent radiochemothetapy and subsequent surgery. Forty radical (R -), six non-radical, and eleven exploratory operations were performed. Pneumonia (live cases), pulmonary insufliciency (one case), bronchial fistuIa (one case) were the major, non- fatal complications. Four deaths due to adult respiratory distress syndrome (ARDS) or pulmonary embolism occurred. Sixty percent ofthe IO patients who had no viable ttmtor at operation survived 3 years, as well as 41% of those who achieved a complete remission by resection and 11% of those with residual disease (R+) alter operation. However, the I- and 2-year survival rates were similar. The main pattern of faihne in R- and R+ patients was extra- and intra-RT-field progression, respectively. A slightly higher rate of postoperative complications, with respect to current practice, was observed However, data lead to argument on the improvement of lowregional control and long-term survival following radical surgery.
Reviews Lung cancer Gilliland FD, Same1 IM. DeporPnent ofMedicine, Cancer Center; New Mexico Univ. School of Medicine, 900 Camino de Salud NE, Albuquerque, NM87131. Cancer Sutv 1994;19-20:175-95. During the 20th century, a dramatic epidemic of lung cancer deaths has occurred in many countries. The time trends of lung cancer incidence and mortality primarily reflect patterns of cigarette smoking, the predominant risk factor, but inconsistencies are evident in international comparisons. Although the predominant role of tobacco smoking as a cause of lung cancer throughout the world is amply documented the persistence of tobacco smoking and the continued penetration of manufactured cigarettes into new markets provide a strong reason for continuing to monitor hmg cancer trends. Changea in other risk f&ctors for lung cancer and changea in diagnostic and death certiiicate reporting practices may also affect trends in rates. However, our tmdemmnding of the relationship between smoking and lung cancer allows forecasting of lung cancer rates for public beahh planning.
12 (1995)
113-160
Nonoperative management of non-small cell lung cancer: The current Cancer and Leukemia Group B experience Green Iwi Kosty MP, Muscato JJ, Graziano S, Dillman RO Clamon GHet al. Division of Hematology/oncoloogy. .%n Diego Medical Cente,: University of CaI$ornia, 200 WArborSt, San Diego, 01 92130. Semin Oncol 1994;21:Suppl6:60-5. The Cancer and Leukemia Group B (CALGB) is studying nonoperative management in two subgroups of patients with advanced non-small cell lung cancer. In patients with regional disease, primarily those with bulky N2 or T4 disease or those with contralateral mediastinal involvement (N3), a phase III trial is under way to explore concurrent carboplatin as intensification of local therapy and additional systemic treatment. This builds on prior CALGB work demonstrating the benefits of induction chemotherapy prior to radiation for selected patients with stage III disease. For patients with still more advanced disease, a trial evaluating etflcacy and cost of two supportive care modalities during intensive chemotherapy is about to begin accrual. Following its completion, the CALGB plans to evaluate new chemotherapy combinations based on one or more of the exciting new agents now being tested for the nonopemtive management of non-small cell lung cancer. The treatment of non-small cell lung cancer: Current perspectives and contmversies, future directions Bunn PA Jr. University of Colorado Cancer Center: Campus Box B188. 4200 E Ninth Ave, Denver, CO 80262. Semin Oncol 1994;2l:Suppl 6149-59. The projected cure rate for patients who develop lung cancer in 1993 is only 13%. The majority of these patients have metastatic disease at the time of diagnosis, and are therefore ineligible for curative stngery. Among the minority of patients who undergo surgical therapy with curative intent, the majority experience relapse in metastatic sites. Patients with metastatic disease cannot be cured with currently available therapies. Recent randomized studies suggest that cisplatin-based chemotherapy regimens can prolong sutvivaI in patients with metasmtic non-small cell lung cancer and small cell lung cancer. It was thus logical to evaluate cisplatinbased chemotherapy in early disease stages. Many randomized studies have compared radiation therapy alone with radiation plus cisplatin-based chemotherapy in locally advanced, inoperable, stages IIIA and IIIB non-small cell lung cancer. Most, but not ah, of these studies show a survival benedit for the combined-modality approach. Although the improvement in median length of survival in these studies is modest, long-term smvival rates are often doubled or tripled. The optimal chemomdiotherapy combination is unknown. Fewer randomized trials have evaluated cisplatin-based chemotherapy as an adjuvant to surgery in operable stages I through IIIA disease. A trial of the Lung Cancer Study Group comparing postoperative cyclopbosphamide/doxotnbicin/cispIatin with immunotherapy in stages II and IIIA adenocarcinoma and large cell carcinoma showed a small snrvival advantage for the chemotherapy. A Enropean postoperative randomized study comparing cisplatin-based chemothempy with no therapy also showed a survival advantage for chemotherapy, as did a small ongoing stndy from M.D. Anderson Cancer Center (Houston, TX) with preoperative chemotherapy. However, there are many negative randomized studies evaluating postoperative chemotherapy, especially with non-cisplatin-based regimens, and further studies are obviously needed. Many new agents have produced exciting prelimimuy results. Response rates in excess of 20% were reported for paclitaxel (TXOI; Bristol-Myers Squibb Company, Princeton, NJ), irinotecan (CPT-II), topotecan, and gemcitabine. Studies in the next few years will help to define the ultimate role of these agents. Further developments in understanding the biology (and molecular biology) of lung cancer are leading to preclinicaI studies of antigrowth factors and genetic therapy.
Abstracts/Lung
Cancer
Multimudality therapy for non-small-cell lung cancer Lilenbaum RC, Green MR UCSD Cancer Centec 200 W&Arbor Drive, Sun Diego, CA 92103-8421. Oncology (USA) 1994;8:25-3 1. The optimal treatment strategy for patients with locally advanced (stage III) non-smallcell lung cancer remains controversial. Primary surgical resection 01 conventional thomcic irradiation alone results in poor longterm survival for the majority of stage III patients. Several multimodality strategies are reviewed in this article. Radiation followed by surgety may increase resectability, but its effects on smvivaJ are unproven. Sequential chemothempy and radiation have demonstrated a survival advantage for selected stage III patients. Chemotherapy followed by surgery has ah shown encouraging results, and additional studies are in progress. Concurrent chemoradiotherapy has shown conllicting results in a few randomized studies. Concurrent chemotherapy and radiation followed by surgery has been tested only in phase II trials and awaits further studies.
Surgery after radiochemotberapy for stage III lung cancer: Postoperative complications and late results Tavecchio L, Ravasi G, Bedini AV, Gramagha A, Milani F. Divisione OCT. lstituto Nazionole Tumori, Ma G Venezion I. 20133Milan. J Surg OncoI 1994;56:2-6. Fifty-seven stage III lung cancer patients underwent radiochemothetapy and subsequent surgery. Forty radical (R -), six non-radical, and eleven exploratory operations were performed. Pneumonia (live cases), pulmonary insufliciency (one case), bronchial fistuIa (one case) were the major, non- fatal complications. Four deaths due to adult respiratory distress syndrome (ARDS) or pulmonary embolism occurred. Sixty percent ofthe IO patients who had no viable ttmtor at operation survived 3 years, as well as 41% of those who achieved a complete remission by resection and 11% of those with residual disease (R+) alter operation. However, the I- and 2-year survival rates were similar. The main pattern of faihne in R- and R+ patients was extra- and intra-RT-field progression, respectively. A slightly higher rate of postoperative complications, with respect to current practice, was observed However, data lead to argument on the improvement of lowregional control and long-term survival following radical surgery.
Reviews Lung cancer Gilliland FD, Same1 IM. DeporPnent ofMedicine, Cancer Center; New Mexico Univ. School of Medicine, 900 Camino de Salud NE, Albuquerque, NM87131. Cancer Sutv 1994;19-20:175-95. During the 20th century, a dramatic epidemic of lung cancer deaths has occurred in many countries. The time trends of lung cancer incidence and mortality primarily reflect patterns of cigarette smoking, the predominant risk factor, but inconsistencies are evident in international comparisons. Although the predominant role of tobacco smoking as a cause of lung cancer throughout the world is amply documented the persistence of tobacco smoking and the continued penetration of manufactured cigarettes into new markets provide a strong reason for continuing to monitor hmg cancer trends. Changea in other risk f&ctors for lung cancer and changea in diagnostic and death certiiicate reporting practices may also affect trends in rates. However, our tmdemmnding of the relationship between smoking and lung cancer allows forecasting of lung cancer rates for public beahh planning.
12 (1995)
113-160
Nonoperative management of non-small cell lung cancer: The current Cancer and Leukemia Group B experience Green Iwi Kosty MP, Muscato JJ, Graziano S, Dillman RO Clamon GHet al. Division of Hematology/oncoloogy. .%n Diego Medical Cente,: University of CaI$ornia, 200 WArborSt, San Diego, 01 92130. Semin Oncol 1994;21:Suppl6:60-5. The Cancer and Leukemia Group B (CALGB) is studying nonoperative management in two subgroups of patients with advanced non-small cell lung cancer. In patients with regional disease, primarily those with bulky N2 or T4 disease or those with contralateral mediastinal involvement (N3), a phase III trial is under way to explore concurrent carboplatin as intensification of local therapy and additional systemic treatment. This builds on prior CALGB work demonstrating the benefits of induction chemotherapy prior to radiation for selected patients with stage III disease. For patients with still more advanced disease, a trial evaluating etflcacy and cost of two supportive care modalities during intensive chemotherapy is about to begin accrual. Following its completion, the CALGB plans to evaluate new chemotherapy combinations based on one or more of the exciting new agents now being tested for the nonopemtive management of non-small cell lung cancer. The treatment of non-small cell lung cancer: Current perspectives and contmversies, future directions Bunn PA Jr. University of Colorado Cancer Center: Campus Box B188. 4200 E Ninth Ave, Denver, CO 80262. Semin Oncol 1994;2l:Suppl 6149-59. The projected cure rate for patients who develop lung cancer in 1993 is only 13%. The majority of these patients have metastatic disease at the time of diagnosis, and are therefore ineligible for curative stngery. Among the minority of patients who undergo surgical therapy with curative intent, the majority experience relapse in metastatic sites. Patients with metastatic disease cannot be cured with currently available therapies. Recent randomized studies suggest that cisplatin-based chemotherapy regimens can prolong sutvivaI in patients with metasmtic non-small cell lung cancer and small cell lung cancer. It was thus logical to evaluate cisplatinbased chemotherapy in early disease stages. Many randomized studies have compared radiation therapy alone with radiation plus cisplatin-based chemotherapy in locally advanced, inoperable, stages IIIA and IIIB non-small cell lung cancer. Most, but not ah, of these studies show a survival benedit for the combined-modality approach. Although the improvement in median length of survival in these studies is modest, long-term smvival rates are often doubled or tripled. The optimal chemomdiotherapy combination is unknown. Fewer randomized trials have evaluated cisplatin-based chemotherapy as an adjuvant to surgery in operable stages I through IIIA disease. A trial of the Lung Cancer Study Group comparing postoperative cyclopbosphamide/doxotnbicin/cispIatin with immunotherapy in stages II and IIIA adenocarcinoma and large cell carcinoma showed a small snrvival advantage for the chemotherapy. A Enropean postoperative randomized study comparing cisplatin-based chemothempy with no therapy also showed a survival advantage for chemotherapy, as did a small ongoing stndy from M.D. Anderson Cancer Center (Houston, TX) with preoperative chemotherapy. However, there are many negative randomized studies evaluating postoperative chemotherapy, especially with non-cisplatin-based regimens, and further studies are obviously needed. Many new agents have produced exciting prelimimuy results. Response rates in excess of 20% were reported for paclitaxel (TXOI; Bristol-Myers Squibb Company, Princeton, NJ), irinotecan (CPT-II), topotecan, and gemcitabine. Studies in the next few years will help to define the ultimate role of these agents. Further developments in understanding the biology (and molecular biology) of lung cancer are leading to preclinicaI studies of antigrowth factors and genetic therapy.