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Metastatic non-small cell lung cancer
150
Abstracts/Lung
Cancer II (1994)
of oncogeoes such as ras has led to new prognostic markets. The discoveryofthelossof suppressorgenes suchasP ~nchromos~m.~ 17 and other genes on chromosome 3p has led to new theories of pathogenesis and new potential intervention strategies. The discovery of changes in cell surface antigen express has led to new tools for early detection, staging, and a potential means to target therapy using moooclonal antibodies. Tbe discovery of peptide and other growth factors is leading to new treatment nod prevention strategies. Cbemopreveotiooagentssuchas 13-cis-retinoicacidambeingevaluated for their potential to prevent lung cancer in high-risk patients. In surgicallyresectablepntients,cisplatin-besadregimeasarebemgevaluated in the neoadjuvant and adjuvant settings. In locally inoperable patients, new ways of combining cisplatin-based regimens and radiotherapy are prolonging survival; further evaluation is under way. The role of postchemotherapy surgery also is being evaluated in Phase111studies for them patients. In metastatic disease, cisplatin-based regimens appear to have made a small impact on survival and new active agents have been discovered. These will be combined with cisplatin-based regimens in future trials. Combined etoposide and cisplatin has produced results equivalent or superior to any other regimen with considerably less toxicity. This two-drug regimen can be considered standard therapy for patients with limited and extensive small cell lung cancer and with inoperable NSCLC. We can proceed through the 1990s with the hope that the advances of the 1980s will yield a significant reduction in lung cancer mortality rates.
New treatment opportunities in non-small cell lung cancer Van Zandwijk N. Rodenhuis S. Mooi W.J. Department of Medical Onculogy, Netherlands Cancer Institute, Pksmanlaan 121, 1066 CX Amrreraknz.Lung Cancer (Ireland) 1993;9 Suppl2:S109-16. We have investigated the clinical importance of K-ras oocogeoe activation and the expression of the neural cell adhesion molecule (NCAM) in a series of surgically -ted lung carcinomsa. In patients with inoperable disease we correlated pretreatment levels of serum neuronspecific enolase (NSE) and lactate debydrogenase (LDH) with response to chemotherapy. The presence of K- ras point mutations and N-CAM expression, as measured by Mab 123C3 immunostaining, defined subgroups of patients with non-small cell lung cancer (adenccarcinoma) for whom the prognosis is poor and disease-free survival is not usually long despite radical resection. In the patients with inoperable disease high NSE and LDH levels correlated with an increased response (a0 46) to chemotherapy. The understanding of basic biologic characteristics of non-smallcelllungcancer, i.e. K-raspointmutatioosandneutoendocrine differentiation, may aid in treatment selection and help to identify groups of patients that will benefit from adjuvant chemotherapy.
Me&static non-small cell lung cancer Ettinger DS. Johns Hopkins Oncology Center, 600 N. Wage St, Baltimore, MD 21205. Lung Cancer (Ireland) 1993;9 Suppl2:S69-79. Controversy persists as to whethersystemic chemotherapy is beneficial treatment for stageIV non-small cell lung cancer (NSCLC). Combination chemotherapy used to treat patients with metastatic NSCLC is not associated with long-term survival. Nevertheless, a survival benefit has been demonstrated in patients receiving chemotherapy compared with those receiving supportive care, although in the majority of studies, tbe benefithasnotbeensignificant. NSCLCpatientswithagoodperformance status, no significant weight loss, and adequate bone marrow, liver, and renal function have the best chance of responding to chemotherapy and increasing their survival times. Further studies are needed to identify new active agents and us&l combination chemotherapy regimens to
123-150
treat NSCLC. Both the physician and the patient must weigh the risks and benefits of chemotherapy available to NSCLC.
Treatment of locally advanced non-small cell lung cancer Booomi P. Clinical flairs Med. Oncology Sec., Rush University Medical Center, 1725 West Harrison, Chicago, lL 60612. Lung Cancer (Ireland) 1993;9 Suppl2S49-60. In this review the following topics are discussed: the complexities of Clinical staging in locally advanced non-small cell lung cancer, the results of Phase III non-surgical combined modality studies, the results of Phase II neoadjuvant surgical trials. Although there have been conflicting results, most studies comparing survival of patients with clinical Stages IIIAand IIIB lung cancer have shown significant survival differences between these stage groups. It also appears that patients whose clinical stage is T3,NO may have the beat prognosis and may be the group most likely to benefit liom combined-modality treatment. Additional staging data based on tindmgs at mediastinoscopy are needed to confirm this initial observation. Sequential treatment with cisplatincontaining combination chemotherapy followed by radiation appears to produce a modest increase in 2-year survival rates Further information regarding the effectiveness of this treatment sequence will be provided by a large, ongoing randomized trial comparing radiation alone versus two courses of vinblastine/cisplatin, followed by thoracic irradiation. In a recently reported study thoracic irradiation and concurrent daily cisplatin have produced significantly better survival than radiation alone or radiation combined with weekly cisplatin. Phase III trials of radiation and concurrent combination chemotherapy - particularly etoposide and platinum - should also be done. Both mitomycin/vinblastinene/cisplatin and etoposide/cisplatin given with concurrent thoracic irradiation have produced relatively high response rates and encouraging survival results when given prior to pulmonary resection in patients with Stage IIIA nonsmall cell lung cancer. However, coocern about toxicity has resulted in the deletion of mitomycin from an ongoing Phase III trial testing preoperative chemotherapy. In contrast, Phase II trials of preoperative etoposide/cisplatin plus radiation have produced relatively high response rateswithacceptabletoxicity. Theseobsetvatiooshave IedtheSoutbwest Oncology Gmup to propose the development of a Phase III trial testing this regimen as preoperative treatment. Rationale for the treatment of non-small cell lung cancer Evans WK. Onawa Regional Cancer Centre. 190 h4elrose Awnue, Ottawa, Onr. KlY4K7. Lung Cancer (Ireland) 1993;9 Suppl2:S5-14. The vast numbers of patients with non-small cell lung cancer (NSCLC) worldwide deserve more than the prevailing attitude Of therapeutic nihilism. Although 5-year survival for all but Stage I NSCLC patients is poor, the cumulative evidence from randomized trials of chemotherapy in patients with advanced disease suggests that a very modest increase in median survival time is possible and that a small number of patients survive to 2 years. Furthermore, trials that have evaluated the effect of chemotherapy on cancer- related symptoms have shown a far greater proportion of patients benefiting from symptom relief tbsn would have been surmised from the usually reported objective response rates. More effective supportive care measumshavedramaticallyreducedtbetYequencyofintolerable~trelated side effects, making a trial of chemotherapy a more.reasonable proposition for the symptomatic, good performance status patient. finally, an economic analysis of thecosts of chemotherapy in the setting of advanced NSCLC has demonstrated that the cost of treatment may actually be less than best supportive care in some instancea and, in any event, tbe-costsofchemotherapyarenotexcessivelyexpensivewmpared with many other commonly accepted nononcologic medical practices.
Abstracts/Lung
Cancer II (1994)
of oncogeoes such as ras has led to new prognostic markets. The discoveryofthelossof suppressorgenes suchasP ~nchromos~m.~ 17 and other genes on chromosome 3p has led to new theories of pathogenesis and new potential intervention strategies. The discovery of changes in cell surface antigen express has led to new tools for early detection, staging, and a potential means to target therapy using moooclonal antibodies. Tbe discovery of peptide and other growth factors is leading to new treatment nod prevention strategies. Cbemopreveotiooagentssuchas 13-cis-retinoicacidambeingevaluated for their potential to prevent lung cancer in high-risk patients. In surgicallyresectablepntients,cisplatin-besadregimeasarebemgevaluated in the neoadjuvant and adjuvant settings. In locally inoperable patients, new ways of combining cisplatin-based regimens and radiotherapy are prolonging survival; further evaluation is under way. The role of postchemotherapy surgery also is being evaluated in Phase111studies for them patients. In metastatic disease, cisplatin-based regimens appear to have made a small impact on survival and new active agents have been discovered. These will be combined with cisplatin-based regimens in future trials. Combined etoposide and cisplatin has produced results equivalent or superior to any other regimen with considerably less toxicity. This two-drug regimen can be considered standard therapy for patients with limited and extensive small cell lung cancer and with inoperable NSCLC. We can proceed through the 1990s with the hope that the advances of the 1980s will yield a significant reduction in lung cancer mortality rates.
New treatment opportunities in non-small cell lung cancer Van Zandwijk N. Rodenhuis S. Mooi W.J. Department of Medical Onculogy, Netherlands Cancer Institute, Pksmanlaan 121, 1066 CX Amrreraknz.Lung Cancer (Ireland) 1993;9 Suppl2:S109-16. We have investigated the clinical importance of K-ras oocogeoe activation and the expression of the neural cell adhesion molecule (NCAM) in a series of surgically -ted lung carcinomsa. In patients with inoperable disease we correlated pretreatment levels of serum neuronspecific enolase (NSE) and lactate debydrogenase (LDH) with response to chemotherapy. The presence of K- ras point mutations and N-CAM expression, as measured by Mab 123C3 immunostaining, defined subgroups of patients with non-small cell lung cancer (adenccarcinoma) for whom the prognosis is poor and disease-free survival is not usually long despite radical resection. In the patients with inoperable disease high NSE and LDH levels correlated with an increased response (a0 46) to chemotherapy. The understanding of basic biologic characteristics of non-smallcelllungcancer, i.e. K-raspointmutatioosandneutoendocrine differentiation, may aid in treatment selection and help to identify groups of patients that will benefit from adjuvant chemotherapy.
Me&static non-small cell lung cancer Ettinger DS. Johns Hopkins Oncology Center, 600 N. Wage St, Baltimore, MD 21205. Lung Cancer (Ireland) 1993;9 Suppl2:S69-79. Controversy persists as to whethersystemic chemotherapy is beneficial treatment for stageIV non-small cell lung cancer (NSCLC). Combination chemotherapy used to treat patients with metastatic NSCLC is not associated with long-term survival. Nevertheless, a survival benefit has been demonstrated in patients receiving chemotherapy compared with those receiving supportive care, although in the majority of studies, tbe benefithasnotbeensignificant. NSCLCpatientswithagoodperformance status, no significant weight loss, and adequate bone marrow, liver, and renal function have the best chance of responding to chemotherapy and increasing their survival times. Further studies are needed to identify new active agents and us&l combination chemotherapy regimens to
123-150
treat NSCLC. Both the physician and the patient must weigh the risks and benefits of chemotherapy available to NSCLC.
Treatment of locally advanced non-small cell lung cancer Booomi P. Clinical flairs Med. Oncology Sec., Rush University Medical Center, 1725 West Harrison, Chicago, lL 60612. Lung Cancer (Ireland) 1993;9 Suppl2S49-60. In this review the following topics are discussed: the complexities of Clinical staging in locally advanced non-small cell lung cancer, the results of Phase III non-surgical combined modality studies, the results of Phase II neoadjuvant surgical trials. Although there have been conflicting results, most studies comparing survival of patients with clinical Stages IIIAand IIIB lung cancer have shown significant survival differences between these stage groups. It also appears that patients whose clinical stage is T3,NO may have the beat prognosis and may be the group most likely to benefit liom combined-modality treatment. Additional staging data based on tindmgs at mediastinoscopy are needed to confirm this initial observation. Sequential treatment with cisplatincontaining combination chemotherapy followed by radiation appears to produce a modest increase in 2-year survival rates Further information regarding the effectiveness of this treatment sequence will be provided by a large, ongoing randomized trial comparing radiation alone versus two courses of vinblastine/cisplatin, followed by thoracic irradiation. In a recently reported study thoracic irradiation and concurrent daily cisplatin have produced significantly better survival than radiation alone or radiation combined with weekly cisplatin. Phase III trials of radiation and concurrent combination chemotherapy - particularly etoposide and platinum - should also be done. Both mitomycin/vinblastinene/cisplatin and etoposide/cisplatin given with concurrent thoracic irradiation have produced relatively high response rates and encouraging survival results when given prior to pulmonary resection in patients with Stage IIIA nonsmall cell lung cancer. However, coocern about toxicity has resulted in the deletion of mitomycin from an ongoing Phase III trial testing preoperative chemotherapy. In contrast, Phase II trials of preoperative etoposide/cisplatin plus radiation have produced relatively high response rateswithacceptabletoxicity. Theseobsetvatiooshave IedtheSoutbwest Oncology Gmup to propose the development of a Phase III trial testing this regimen as preoperative treatment. Rationale for the treatment of non-small cell lung cancer Evans WK. Onawa Regional Cancer Centre. 190 h4elrose Awnue, Ottawa, Onr. KlY4K7. Lung Cancer (Ireland) 1993;9 Suppl2:S5-14. The vast numbers of patients with non-small cell lung cancer (NSCLC) worldwide deserve more than the prevailing attitude Of therapeutic nihilism. Although 5-year survival for all but Stage I NSCLC patients is poor, the cumulative evidence from randomized trials of chemotherapy in patients with advanced disease suggests that a very modest increase in median survival time is possible and that a small number of patients survive to 2 years. Furthermore, trials that have evaluated the effect of chemotherapy on cancer- related symptoms have shown a far greater proportion of patients benefiting from symptom relief tbsn would have been surmised from the usually reported objective response rates. More effective supportive care measumshavedramaticallyreducedtbetYequencyofintolerable~trelated side effects, making a trial of chemotherapy a more.reasonable proposition for the symptomatic, good performance status patient. finally, an economic analysis of thecosts of chemotherapy in the setting of advanced NSCLC has demonstrated that the cost of treatment may actually be less than best supportive care in some instancea and, in any event, tbe-costsofchemotherapyarenotexcessivelyexpensivewmpared with many other commonly accepted nononcologic medical practices.