[Immunotherapy of Bronchogenic Carcinoma and Its Perspectives]. / Imunoterapie u bronchogenního karcinomu a její perspektivy.

Immunotherapy is becoming another possible alternative in the treatment of lung cancer. It is a completely different method of treating cancer which is not directed to the tumor itself, but to the immune system. Surface antigens present on tumor cells may be an effective and specific therapeutic targets and strategies based on antibodies inhibiting immune check-points significantly improves the antitumor immune response. Monoclonal antibody blocking CTLA 4 (cytotoxic T-lymphocyte antigen) and PD 1 receptor (protein programmed cell death) and its ligand PD L1 showed clinical efficacy and nivolumab (antiPD 1) was approved in 2nd line treatment squamous nonsmall cell lung cancer.

New aspects of photodynamic therapy for central type early stage lung cancer.

BACKGROUND: and Objective Photodynamic therapy (PDT) has come to be considered as the first choice of treatment for central type early stage lung cancer (CELC). Recent advances in the ability to diagnose CELC, and in photosensitizers, as well as sophisticated clinical management, may improve the therapeutic outcome and expand the indications of PDT. MATERIALS AND METHODS: We made the search for papers on PDT for lung cancer to select the most relevant articles. Based on this review and our recent data, we discussed the best available evidence for the diagnosis, the definition of indications, photosensitizers, and clinical management with regard to PDT. RESULTS: To obtain complete response (CR) by PDT, the selection of the indications is extremely important, including the extent of the tumor on the bronchial surface and the depth of invasion in the bronchial wall. The development of autofluorescence bronchoscopy (AFB) and endobronchial ultrasonography (EBUS) have had a large impact on diagnostic bronchoscopy for CELC. CELCs less than 1 cm in diameter showed a favorable cure rate by PDT, thus this is a good indication for PDT. The relatively newer photosensitizer NPe6, which has a stronger antitumor effect than Photofrin, showed similar treatment outcome even for large tumors >1.0 cm in diameter. Furthermore, comprehensive management including photodynamic diagnosis before and after PDT should be effective to minimize the possibility of local recurrence after PDT. CONCLUSION: The present guidelines of PDT for CELC were established based on the data obtained from studies in the 1980's. We postulate that comprehensive diagnosis and the new generation of photosensitizers may increase the CR rate and expand the indications of PDT for larger tumors.

Efficacy and safety of Shen-Ling-Bai-Zhu-San combined with chemotherapy for lung cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Lung cancer (LC), with the high incidence in malignant tumors in the world, and seriously affects people's lives and brings a great economic burden. Previous clinical studies on Shen-Ling-Bai-Zhu-San (SLBZS) combined with chemotherapy for the treatment of lung cancer have been increasing, but there are no systematic reviews. This study aims to systematically study the efficacy and safety of SLBZS combined with chemotherapy in the treatment of LC. METHODS: The Chinese and English databases will be searched by us for related documents, and the search time limit is January 2021. Databases including PubMed, Embase, Web of Science, the Cochrane Library, Chinese databases include China National Knowledge Infrastructure, Wanfang Data, ChongqingVIP Information Resource Integration Service Platform, China Biomedical Literature. The international clinical trial registration platform and the Chinese clinical trial registration platform will be searched by us to find ongoing or unpublished trials. After screening the literature based on inclusion and exclusion criteria, 2 researchers independently extracted data. The primary outcomes were the treatment efficiency. RevMan 5.3.5 software will be used for statistical analysis. The Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to evaluate the quality evidence of each result. RESULTS: This study will provide the latest evidence for the SLBZS combined with chemotherapy for LC. CONCLUSION: The efficacy and safety of SLBZS combined with chemotherapy for LC will be evaluated. UNIQUE INPLASY NUMBER: INPLASY202110025.

Chemotherapy resistance research of lung cancer based on micro-fluidic chip system with flow medium.

Micro total analysis systems (-TAS) or labs-on-achip, have been spreading rapidly due to their desirable characteristics, including reductions in reagent consumption, space requirements and analysis time. This work aimed at establishing an integrated microfluidic system which can supply the cells with fresh medium of oxygen and nutrition continuously at a control flow rate mimicking the microenvironment in vivo. Human non-small cell lung cancer cell line SPCA1 was seeded in a microchip supplied with fresh medium at a constant rate of 15 mm/24 h controlled by a pump. The expression of P-gp for verapamil-pretreated or non-pretreated cells was assayed with immunofluorescence. Both groups cells were exposed to anticancer drug VP-16 at 30 microM for 6 h before the apoptosis analysis online. The results indicated that the cells could grow and spread well for 4 days in the microfluidic system successively furnished with fresh medium. Immunofluorescence assay showed that the intensity of the fluorescence for the verapamil-pretreated cells was obvious weak compared with that of nonpretreated cells. Apoptosis analysis demonstrated that the percentage of apoptotic cells for verapamil-pretreated group increased around twofold compared with that of nonverapamil pretreated group (26.5+/-2.5% versus 10.9+/- 0.85%, p<0.05), showing a similar results as by flow cytometry analysis. All these indicate that P-gp plays an important role in the resistance to VP-16 in SPCA1, the microfluidic system provides a suitable environment for cells survival and is valuable in long time cell culture and bioassays mimicking the microenvironment in vivo and deserved to be studied further.

PD-1/PD-L1 negative schwannoma mimicking obstructive bronchial malignancy: A case report.

Schwannomas are homogeneous tumors of schwann cells and occur at peripheral and cranial nerves on the upper limbs, the head and neck area. Rarely, a bronchial schwannoma may appear in the lung and be misdiagnosed as lung neoplasms. Here, we report a 56-year old woman with a 5.8 × 7.0 × 2.8 cm lesion in her right upper lobe bronchus. The lesion had a maximum standardized uptake value (SUVmax ) of 8.5 by 18-fluorodeoxyglucose positron emission tomography (FDG-PET). Bronchoscopy showed a mass obstructing the bronchus that bled easily. Despite repeated biopsies, a lung malignancy could not be excluded, and surgical resection was subsequently performed. Pathological examination demonstrated a primary bronchial schwannoma that was positive for molecular markers S-100 and SOX-10, negative for immune checkpoint marker PD-1/PD-L1 but also demonstrated certain uncommon pathological features. This case highlights the heterogeneity of bronchial masses and the diagnostic challenge for differentiating benign and malignant tumors in the thorax. KEY POINTS: Rare bronchial schwannoma mimics lung malignancy and poses a diagnostic challenge. This case of bronchial schwannoma, unlike peripheral schwannoma, lacks PD-L1. Pathological features indicate autonomic nerve origin for pulmonary schwannomas.

[Surgical management of bevacizumab-associated peritonitis due to perforation]. / Chirurgisches Management der perforationsbedingten Peritonitis im Zusammenhang mit einer Bevacizumab-Therapie.

INTRODUCTION: Bevacizumab (Avastin, Fa. Roche, Genentech) is the first anti-angiogenic agent to be approved for the routine clinical treatment of cancer. Its toxicity profile is different to that of standard chemotherapeutic substances. Despite the rarity of gastrointestinal (GI) perforation in patients treated with bevacizumab, this serious adverse event results in significant morbidity and mortality. It was the aim of this study, based on exemplary cases of the reporting clinic as well as on published experiences, to characterise the specific clinical findings, the extraordinary pathogenesis, and the therapeutic outcome of such cases of peritonitis caused by perforation after antibody treatment. METHODS: Data of all patients with perforation-caused peritonitis due to bevacizumab therapy since its clinical inauguration were sought in i) the database of the reporting clinic (case series), ii) in the published literature for comparison (historical comparative group) and iii) analysed with regard to results of the surgical management (evaluated parameters: rate of anastomotic insufficiency / disturbances of wound healing, morbidity, mortality). RESULTS: Over a time period of 4 years (from 2 / 1 / 2004 to 1 / 31 / 2008), overall 15 patients were found in this study, among whom 4 patients came from the reporting clinic (mean age, 57 years; males : females = 2 : 2). The mean duration of antibody (Ab) treatment until occurrence of the complication was 70 days (range: 8-150 days). Thirteen patients underwent surgical intervention, 2 patients died due to severe peritonitis without any operation. The overall morbidity was 73.3 % (n = 11 / 15), the mortality was 33.3 % (n = 5 / 15). All patients with an anastomosis developed an anastomotic insufficiency (100 %). Wound healing complications occurred in 38.5 % of the subjects (n = 5 / 13). CONCLUSIONS: Peritonitis after GI perforation due to bevacizumab-based Ab treatment needs to be considered as a rare but serious and life-threatening complication. Impairment of wound healing because of the inhibition of angiogenesis is the reason for a different management of GI perforation under these conditions compared with the standard surgical treatment of peritonitis of other causes. In particular, it is recommended to avoid primary anastomosis and to prefer application of an intestinal stoma.

[Bilateral uveitis associated with nivolumab therapy]. / Uvéite bilatérale associée à un traitement par nivolumab.

Immune-related adverse events (IRAEs) are rare but serious adverse events that may be associated with inhibitors of few immune control points. The purpose here is to report the case of an inflammatory ocular disease, potentially linked to the immunity and use of nivolumab, a new immunological agent used for the treatment of a solid tumor. In spite of the involvement of this treatment in the onset of inflammation, we must always seek another cause. It is possible to continue this treatment by considering the benefit/risk balance for each patient. Close collaboration between oncologists and ophthalmologists is necessary in the diagnosis and rapid management of these IRAE ocular related to these new emerging therapies.

Soluble Triggering Receptor Expressed on Myeloid Cells 1 in lung cancer.

Soluble Triggering Receptor Expressed on Myeloid Cells 1 (sTREM-1) can be found in the sera of patients with infectious, autoimmune and malignant diseases. The primary objective of this study was to investigate the prognostic significance of sTREM-1 in lung cancer patients. We analyzed the sera of 164 patients with lung cancer of all histologies and all stages at the time of diagnosis. We employed an ELISA using the anti-TREM-1 clone 6B1.1G12 mAb and recombinant human TREM-1. Patient data was collected retrospectively by chart review. In ROC-analysis, a sTREM-1 serum level of 163.1 pg/ml showed the highest Youden-Index. At this cut-off value sTREM-1 was a marker of short survival in patients with NSCLC (median survival 8.5 vs. 13.3 months, p = 0.04). A Cox regression model showed stage (p < 0.001) and sTREM-1 (p = 0.011) to indicate short survival. There were no differences in sTREM-1 serum values among patients with or without infection, pleural effusion or COPD. sTREM-1 was not associated with metastasis at the time of diagnosis and was not a predictor of subsequent metastasis. In SCLC patients sTREM-1 levels were lower than in NSCLC patients (p = 0.001) and did not predict survival. sTREM-1 did not correlate with CRP or the number of neutrophils. In non-small cell lung cancer patients, sTREM-1 in serum has prognostic significance.

Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages

Background: Bronchogenic carcinoma (lung cancer) is one of the leading causes of death. Although many compounds isolated from natural products have been used to treat it, drug resistance is a serious problem, and alternative anti-cancer drugs are required. Here, melittin from Apis mellifera venom was used, and its effects on bronchogenic carcinoma cell proliferation and tumour-associated macrophage differentiation were evaluated. Methods: The half maximal inhibitory concentration (IC50) of melittin was measured by MTT. Cell death was observed by annexin V and propidium iodide (PI) co-staining followed by flow cytometry. Cell cycle arrest was revealed by PI staining and flow cytometry. To investigate the tumour microenvironment, differentiation of circulating monocytes (THP-1) into tumour-associated macrophages (TAMs) was assayed by sandwich-ELISA and interleukin (IL)-10 levels were determined. Cell proliferation and migration was observed by flat plate colony formation. Secretion of vascular endothelial growth factor (VEGF) was detected by ELISA. The change in expression levels of CatS, Bcl-2, and MADD was measured by quantitative RT-PCR. Results: Melittin was significantly more cytotoxic (p < 0.01) to human bronchogenic carcinoma cells (ChaGo-K1) than to the control human lung fibroblasts (Wi-38) cells. At 2.5 µM, melittin caused ChaGo-K1 cells to undergo apoptosis and cell cycle arrest at the G1 phase. The IL-10 levels showed that melittin significantly inhibited the differentiation of THP-1 cells into TAMs (p < 0.05) and reduced the number of colonies formed in the treated ChaGo-K1 cells compared to the untreated cells. However, melittin did not affect angiogenesis in ChaGo-K1 cells. Unlike MADD, Bcl-2 was up-regulated significantly (p < 0.05) in melittin-treated ChaGo-K1 cells. Conclusion: Melittin can be used as an alternative agent for lung cancer treatment because of its cytotoxicity against ChaGo-K1 cells and the inhibition of differentiation of THP-1 cells into TAMs.

The interactive transcript abundance index [c-myc*p73alpha]/[p21*Bcl-2] correlates with baseline level of apoptosis and response to CPT-11 in human bronchogenic carcinoma cell lines.

Currently available cytotoxic chemotherapy is ineffective for treating bronchogenic carcinoma, and this is partly due to unpredictable inter-tumor variation in resistance. For example, tumors with inactivating p53 mutations or deletions are less likely to respond to certain chemotherapeutics. However, even if p53 is intact, a tumor may be unresponsive if defects in other p53 pathway genes compromise apoptosis. In an effort to identify biomarkers that better predict response to camptothecin, we investigated the association of CPT-11 (irinotecan)-induced cytotoxicity (IC50) with apoptosis or expression of genes upstream or downstream of p53 in cell lines that retain wild-type p53. CPT-11 response was greater in cell lines with higher baseline apoptosis (p<0.05). In addition, the interactive transcript abundance index (ITAI) [c-myc*p73alpha]/[p21*Bcl-2] was directly correlated with baseline apoptosis (p<0.01) and CPT-11 response (p<0.05). The ITAI was also correlated with CPT-11 response among cell lines derived from a variety of tissues that had inactivating p53 mutations or deletions, supporting its applicability for predicting response to camptothecins in other tissues regardless of p53 status.

[Clinical and molecular predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer]. / Facteurs prédictifs de la réponse aux inhibiteurs de tyrosine kinase ciblant le récepteur à l'EGF dans le cancer bronchique.

Up to 10% of patients with non-small cell lung carcinoma (NSCLC) achieve an objective response to EGFR tyrosine kinase inhibitors (EGFR-TKI) such as erlotinib or gefitinib. This rate of response is related to non-smoker status, female gender, adenocarcinoma subtype, and Asian ethnicity. Molecular analysis showed that EGFR tyrosine kinase domain somatic mutations appear to be a strong predictor of response to EGFR-TKI. The L858R point mutation and the E746-A750 deletion represent 90% of the mutations encountered in responding patients. The amplification of EGFR gene also seems to be predictive of the response to EGFR-TKI, whereas T790M point mutation induces secondary resistance to EGFR-TKI. Nevertheless, objective responses or strong long-term stabilizations are observed in patients without any EGFR abnormality. Thus, the assessment of the EGFR status in patients with NSCLC remains controversial for clinical practice. The assessment of EGFR abnormalities should be targeted to identify reliable biomarkers of the NSCLC response to EGFR-TKI. This review presents the current knowledge on predictive biomarkers of NSCLC response to EGFR-TKI and the methods available for the assessment of EGFR status.

[The place of targeted therapies in the management of non-small cell bronchial carcinoma. Methodology of the development of targeted therapies in pulmonary oncology]. / La place des thérapeutiques ciblées dans la prise en charge des CBNPC. Méthodologie du développement des thérapeutiques ciblées en cancérologie pulmonaire.

The development of new anticancer agents specifically targeting the molecular processes involved in carcinogenesis is a major step forward in the treatment of patients with lung cancer. Preclinical models often show a cytostatic mechanism of action and predict an improved toxicity profile compared to traditional cytostatic drugs. This means that a standard development design based upon tumour shrinkage is not appropriate for these agents. The development of targeted therapies requires a new model for clinical phase I and II trials, with careful selection of patients who might benefit from treatment and adapted endpoints to establish that growth inhibition can be translated into a clinical benefit. Some targeted agents may have been discarded because of the use of inappropriate traditional endpoints during their development. A greater investment with additional implementation of correlative translational and pharmacodynamic studies during early development is crucial before going to phase III trials.

[Evaluation criteria for bronchial carcinoma. Economic criteria in the management of lung cancer]. / Critères d'évaluation des cancers broncho-pulmonaires. Quels critères économiques?

The economic assessment of treatments or medical strategies has been the subject of an increasing number of publications. The elevated costs and modest efficacy of many treatments for lung cancer are an added impetus to such analyses. This review summarises the principal results of these analyses, the limitations of the methods used and discusses the evaluation of the cost of these cancers to society. The economic assessment of new chemotherapeutic drugs, and the place of cost-effectiveness analysis in randomized trials is also considered. In the final part, we outline future prospects for this area of research and the importance of such considerations for clinicians. These evaluations, which provide complementary data for clinicians when making decisions on therapeutic options, will be adopted more widely in coming years.

The place of targeted therapies in the management of non-small cell bronchial carcinoma. Molecular markers as predictors of tumor response and survival in lung cancer.

This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. The main core of recent research has centered on epidermal growth factor receptor (EGFR) mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine-kinase inhibitors. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine-kinase inhibitors plus aromatase inhibitors. Understanding the relevance of these findings can help to change the clinical practice in oncology towards customizing chemotherapy and targeted therapies, leading to improvement both in survival and in cost-effectiveness.

Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma.

20 patients with advanced non-small cell lung cancer were treated with ifosfamide and mesna 1.5 g/m2 daily for 5 days; 10 received the drug by mouth and 10 i.v. Both schedules resulted in a reduction in the elimination half-life with an increased total and nonrenal clearance of ifosfamide over the 5-day period. Oral administration resulted in an unacceptably high incidence of encephalopathy(5/10) which was not seen in the i.v. group. In two patients this encephalopathy manifested itself as coma which lasted for 24 to 48 h but was fully reversible and in the other three cases as somnolence occurring for more than 50% of the patients' waking hours. Nadir blood counts and response rates were similar in both arms. The encephalopathy suggests that there are metabolic differences between the i.v. and oral routes and that a metabolite rather than the parent drug is responsible for this syndrome. In addition it was shown that the total and nonrenal clearance of the drug was significantly less when the drug was administered orally. None of the pharmacokinetic parameters either singly or in combination predicted for ifosfamide toxicity. No correlation between the creatinine clearance and ifosfamide renal clearance was demonstrated suggesting tubular reabsorption of the drug. In conclusion, ifosfamide cannot be given orally at the conventionally employed i.v. doses.

A Phase I Study of Light Dose for Photodynamic Therapy Using 2-[1-Hexyloxyethyl]-2 Devinyl Pyropheophorbide-a for the Treatment of Non-Small Cell Carcinoma In Situ or Non-Small Cell Microinvasive Bronchogenic Carcinoma: A Dose Ranging Study.

INTRODUCTION: We report a phase I trial of photodynamic therapy (PDT) of carcinoma in situ (CIS) and microinvasive cancer (MIC) of the central airways with the photosensitizer (PS) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH). HPPH has the advantage of minimal general phototoxicity over the commonly used photosensitizer porfimer sodium (Photofrin; Pinnacle Biologics, Chicago, IL). METHODS: The objectives of this study were (1) to determine the maximally tolerated light dose at a fixed photosensitizer dose and (2) to gain initial insight into the effectiveness of this treatment approach. Seventeen patients with 21 CIS/MIC lesions were treated with HPPH with light dose escalation starting from 75 J/cm2 and increasing to 85, 95,125, and 150 J/cm2 respectively. Follow-up bronchoscopy for response assessment was performed at 1 and 6 months, respectively. RESULTS: The rate of pathological complete response (CR) was 82.4% (14 of 17 evaluable lesions; 14 patients) at 1 month and 72.7% (8/11 evaluable lesions; 8 patients) at 6 months. Only four patients developed mild skin erythema. One of the three patients in the 150 J/cm2 light dose group experienced a serious adverse event. This patient had respiratory distress caused by mucus plugging, which precipitated cardiac ischemia. Two additional patients treated subsequently at this light dose had no adverse events. The sixth patient in this dose group was not recruited and the study was terminated because of delays in HPPH supply. However, given the observed serious adverse event, it is recommended that the light dose does not exceed 125 J/cm2. CONCLUSIONS: PDT with HPPH can be safely used for the treatment of CIS/MIC of the airways, with potential effectiveness comparable to that reported for porfimer sodium in earlier studies.

The role of adjuvant surgery in the combined modality therapy of small-cell bronchogenic carcinoma after a chemotherapy-induced partial remission.

Twenty-six patients with a limited-disease presentation of small-cell bronchogenic carcinoma (SCBC) had surgery after achieving a partial remission with three cycles of chemotherapy. Persistent SCBC was found in 15 patients (58%), non-small-cell bronchogenic carcinoma (NSCBC) in six patients (23%), and no malignancy in five patients (19%). Twelve patients have died since surgery. Tumor-node-metastasis (TNM) staging prior to or after chemotherapy was not predictive of outcome, but an N0 status found at pathological examination of the surgical specimen was predictive of long-term survival. Median survival for this group of patients was 25 months. Adjuvant surgery is feasible and may be beneficial.

High-dose intensification therapy with autologous bone marrow support for limited small-cell bronchogenic carcinoma.

The efficacy and toxicity of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) was studied in 32 patients with untreated limited small-cell bronchogenic carcinoma (SCBC). Ten patients received three courses of induction therapy consisting of vincristine (VCR) (1.5 mg X 2), ifosfamide (5 g/m2), and Adriamycin (Ad; Adria Laboratories, Columbus, Ohio) (60 mg/m2). Patients then received two courses of intensification therapy with cyclophosphamide (CYT) (4.5 g/m2), 4' demethyl-epipodophyllotoxin-d-D-ethylidene glucoside (VP-16-213) (600 mg/m2) and VCR (2 mg) with ABMT. Another 22 patients received induction therapy with VCR, CYT (600 mg/m2), Ad (50 mg/m2), and VP-16-213 (180 mg/m2). All 22 patients also received intensification therapy of the same dose of CYT (4.5 g/m2) and VP-16-213 (600 mg/m2). Nine patients also received high-dose methotrexate (MTX), four patients received Ad (40 to 60 mg/m2), and two patients received both Ad and MTX. After intensification, patients received elective prophylactic brain irradiation (3,000 rad) and chest irradiation (5,000 rad). After induction therapy, there were 13 (41%) complete remissions (CR) and 17 (53%) partial remissions (PR). After intensification therapy, there were 22 CRs (69%) and 10 PRs (31%). Median survival for all patients was 14 months (range, 5 to 59+). Of the 13 patients who received intensification therapy in CR, five remain disease free (DF), four for 4 years or longer. Of the nine patients to achieve CR with intensification, only one is DF. No patient died during intensification. In conclusion, intensification with high-dose chemotherapy can increase the CR rate, and this approach is most likely to show long-term benefits in patients with minimal disease (CR) at the beginning of intensification therapy.

Chemotherapy for metastatic non-small-cell bronchogenic carcinoma: EST 2575, generation V--a randomized comparison of four cisplatin-containing regimens.

Between December 1979, and October 1981, the Eastern Cooperative Oncology Group (ECOG) compared four cisplatin-containing regimens in the treatment of patients with metastatic non-small-cell bronchogenic carcinoma (NSCBC). CBP (cyclophosphamide, bleomycin, and cisplatin) and AFP (doxorubicin, 5-fluorouracil, and cisplatin) had shown activity in generation II of this study (EST 2575). These were compared to MVP (mitomycin C, vinblastine, and cisplatin) and CAP (cyclophosphamide, doxorubicin, and cisplatin) which were reported efficacious in single institution studies. A total of 479 previously untreated patients with metastatic NSCBC (ECOG performance status 0, 1, or 2) were entered, and of these, 432 (90%) were evaluable. Although MVP resulted in a higher response rate (5 complete responses [CRs], 22 partial responses [PRs], 26% overall) than CBP (4 CRs, 18 PRs, 20% overall), AFP (0 CRs, 18 PRs, 17% overall), or CAP (1 CR, 23 PRs, 23% overall), the difference was not significant. Survival by treatment did not differ significantly. There were 45 life-threatening and six lethal complications of therapy. Although each of the above regimens offers a modest chance of inducing greater than 50% tumor shrinkage (17% to 26%, 21% overall) the effect that these responses have an overall median survival (21.6 to 23.7 weeks, 22.9 weeks overall) is unclear.