Bronchoalveolar Carcinoma Research Articles

Synchronous B3 thymoma and lung bronchoalveolar carcinoma

The association between thymic tumors and other intrathoracic or extrathoracic neoplasms is relatively rare; the synchronous occurrence of thymoma and bronchoalveolar carcinoma of the lung has never been described so far. A huge B3 cystic thymoma was found at thoracotomy to be associated with stage IV bronchoalveolar carcinoma (intraparenchymal and pleural metastases). The thymic tumor was completely resected; lung cancer was biopsied only for diagnosis and staging purposes. After an uneventful postoperative course the patient underwent chemotherapy; she is still alive and well one year after surgery.

Bronchoalveolar Carcinoma Mistaken as an Interstitial Lung Disease

Bronchoalveolar Carcinoma Mistaken as an Interstitial Lung Disease

Chronische respiratorische Insuffizienz: Rolle der Lungentransplantation

Lung transplantation has been established as an appropriate ultimate treatment strategy in end-stage lung disease, when all conventional therapeutic options have been exhausted. Acute and potentially reversible lung diseases (ARDS, pneumonia) and malignancy (broncho-alveolar carcinoma) are not established indications. Retrospective analyses on the natural course of the disease and new medical treatment options have led to fewer transplantations in recipients with emphysema and idiopathic pulmonary hypertension. In end-stage cystic fibrosis and patients with idiopathic pulmonary fibrosis, alternative treatment options are currently not available and lung transplantation is indicated. The available guidelines for candidate selection should be followed. Internationally, there is a trend towards a benefit-orientated allocation of organs. Recommendations for candidate selection, surgical innovations and, especially, the improved long-term follow-up have led to improved results in the last two decades. Long-term results are, however, still unsatisfactory in comparison to liver and kidney transplantations. The main obstacles to long-term survival and causes of death are chronic allograft dysfunction (bronchiolitis obliterans syndrome, BOS) and infections. In the future, the pathogenesis and treatment options for these two entities should be clarified. A further essential task is to increase the donor pool in the future because the current waiting list mortality is approximately 20 %.

Treatment Outcomes by Tumor Histology in Eastern Cooperative Group Study E4599 of Bevacizumab with Paclitaxel/Carboplatin for Advanced Non-small Cell Lung Cancer

The combination of paclitaxel/carboplatin (PC) and bevacizumab (B) was previously shown to extend overall survival (OS) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). An analysis of survival and safety outcomes based on histology is presented here. Patients with cytologically or histologically confirmed metastatic NSCLC were treated with PC + B (PCB) or PC. Median OS for all patients was determined using Kaplan-Meier methodology. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using an unstratified Cox proportional hazards model. Histology-by-treatment interaction was tested with an unstratified multivariate Cox regression model. A total of 444 patients were randomized to PC, and 434 patients were randomized to PCB (the intent-to-treat population). Median OS times were 10.3 and 12.3 months for PC and PCB, respectively, with an HR for PCB of 0.80 (95% CI: 0.69-0.93). A total of 68.8% of patients had adenocarcinoma histology; 18.9% had "not otherwise specified"; 5.5% had large cell undifferentiated; 2.6% had bronchoalveolar carcinoma; and 3.9% "other." For adenocarcinoma, median OS was 10.3 months for PC treatment (n = 302) and 14.2 months for PCB (n = 300), HR 0.69 (95%CI: 0.58-0.83). Sample sizes for other specific histologic subtypes were too small for meaningful comparisons. Safety profiles among histologies were consistent with the overall safety profile, and there were no unexpected adverse event trends. Addition of B to PC is associated with increased survival in previously untreated patients with nonsquamous NSCLC. Adenocarcinoma was associated with an increased survival benefit of PCB treatment. Data for other histologies are inconclusive, primarily because of small patient sample sizes and large CIs.

Survival and prognostic factors in surgically resected synchronous multiple primary lung cancers

The presence of synchronous multiple primary non-small-cell lung cancers (SMPLC) is a rare condition and the optimal treatment remains unclear. In this study, the survival of surgically treated SMPLC patients and the factors affecting survival were analyzed. Between 2001 and 2008, 26 consecutive patients diagnosed with SMPLC, who had all of their tumors resected, were retrospectively evaluated. Patients, who had bronchoalveolar carcinoma or carcinoid tumors and satellite nodules, were excluded. Prognostic factors were analyzed using univariate and multivariate analyses. The tumors were unilateral in 14 and bilateral in 12 patients. In total, 38 procedures were performed. A complete resection was achieved in 35 (92.1%) procedures. The in-hospital mortality rate was 7.6% (two patients). The overall 5-year survival rate was 49.7%, and the median survival time was 40 months. The 5-year survival rate was 40.6% for unilateral and 62.8% for bilateral SMPLC patients (p = 0.47). Histopathologic tumor type, N1 nodal disease, tumor (T) status, and older age did not influence survival. There was no survival disadvantage for patients, upon whom a sublobar resection had been performed. There was a trend toward poorer survival in patients upon whom a pneumonectomy had been performed (p = 0.12). The 3-year survival rate for patients, who received adjuvant chemotherapy and/or radiotherapy (66.7%), was better than other patients (56.3%). In the multivariate analysis, we found a trend toward poor survival in patients, who received a pneumonectomy, and a trend toward better survival in patients, who received adjuvant therapy (p = 0.05 and p = 0.06). The survival of SMPLC patients, who were treated surgically, was satisfactory. Pneumonectomy was a poor prognostic factor, whereas adjuvant therapy was a good prognostic factor.

EphA2 Mutation in Lung Squamous Cell Carcinoma Promotes Increased Cell Survival, Cell Invasion, Focal Adhesions, and Mammalian Target of Rapamycin Activation

Non-small cell lung cancer (NSCLC) has a poor prognosis and improved therapies are needed. Expression of EphA2 is increased in NSCLC metastases. In this study, we investigated EphA2 mutations in NSCLC and examined molecular pathways involved in NSCLC. Tumor and cell line DNA was sequenced. One EphA2 mutation was modeled by expression in BEAS2B cells, and functional and biochemical studies were conducted. A G391R mutation was detected in H2170 and 2/28 squamous cell carcinoma patient samples. EphA2 G391R caused constitutive activation of EphA2 with increased phosphorylation of Src, cortactin, and p130(Cas). Wild-type (WT) and G391R cells had 20 and 40% increased invasiveness; this was attenuated with knockdown of Src, cortactin, or p130(Cas). WT and G391R cells demonstrated a 70% increase in focal adhesion area. Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. A recurrent EphA2 mutation is present in lung squamous cell carcinoma and increases tumor invasion and survival through activation of focal adhesions and actin cytoskeletal regulatory proteins as well as mTOR. Further study of EphA2 as a therapeutic target is warranted.

Treatment of advanced bronchoalveolar carcinoma with the Hsp90 inhibitor STA-9090.

e18137 Background: Treatment options for bronchoalveolar carcinoma (BAC) include conventional chemotherapy and erlotinib in tumors that harbor activating EGFR mutations. The chaperone Hsp90 regulates the folding, stability and activity of many signal transduction proteins important in NSCLC, including EGFR, KRAS, MET and HER2. STA-9090 is a potent, next-generation Hsp90 inhibitor that is structurally unrelated to the first-generation ansamycin class of Hsp90 inhibitors, such as 17-AAG and IPI-504, and has shown superior activity and an improved safety profile relative to these agents in preclinical studies. Methods: We report the case of a 66-year-old white male with metastatic BAC, treated with STA-9090 on a phase I study. Results: The patient was diagnosed with BAC in 2006. Molecular profiling showed wild type KRAS and EGFR, and EGFR was not amplified on FISH testing. Prior treatment included erlotinib, bevacizumab, carboplatin, paclitaxel, pemetrexed, and topotecan with progression of disease on each, and an investigational rexinoid with a three month stabilization of disease. He enrolled in a phase I solid tumor study of STA-9090, and began weekly infusions at 150 mg/m2 for 3 weeks (followed by a rest week). The treatment was well tolerated, with adverse events of mild diarrhea and moderate hypophosphatemia. Target lesions were reduced by 25% after cycle 4 (SD per RECIST), and that response was maintained. The dose of STA-9090 was increased to 180 mg/m2 starting at Cycle 8 and continues to be well-tolerated through Cycle 11. The 11 month treatment duration compares favorably with the average 2-3 month duration of prior regimens. Conclusions: Reduction in tumor size and prolonged stabilization, and a well-tolerated AE profile are encouraging and support the evaluation of STA-9090 in patients with NSCLC, including BAC. A phase II study of STA-9090 in patients with advanced NSCLC is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Synta

‘Flooding’ of the lungs and severe dyspnea in a patient with bronchoalveolar carcinoma

In this case report, we describe a patient with bronchoalveolar carcinoma that experienced severe bronchorrhea and dyspnea after inhalation of N-acetylcysteine. The adverse reactions occurred both after oral and nebulized administration of N-acetylcysteine, resulting in severe dyspnea and the feeling of 'drowning'. Bronchorrhea has previously been reported as an uncommon but serious complication of bronchoalveolar carcinoma. We strongly suspect the administration of N-acetylcysteine to be implicated, as the complications occurred immediately after administration of this drug. As the patient suffered from hyperhomocysteinemia, we speculate that an additive or synergistic interaction with homocysteine may have been involved as well.

Miliary Pattern on Chest Radiography: TB or not TB?

A 37-year-old nonsmoking Ecuadorian mason presented with a 3-month history of productive cough, fever, night sweats, shortness of breath, and weight loss. His symptoms were becoming progressively worse, with substantial decline in functional ability. He had blood-tinged sputum. Physical examination revealed tachypnea, and chest radiography on admission revealed scattered crackles throughout the right lung fields. Results were positive for the purified protein derivative (tuberculin) test and negative for the acid-fast bacillus smear and cultures. Computed tomography of the chest showed diffuse subcentimeter nodules in both lungs fields and an infrahilar mass in the right lung. Bronchoscopic biopsy of the middle and lower parts of the right lung showed poorly differentiated primary lung adenocarcinoma. Palliative care was accepted, and the patient died approximately 1 month later. The differential diagnosis of miliary pattern on chest radiography includes miliary tuberculosis (TB), histoplasmosis, sarcoidosis, pneumoconiosis, bronchoalveolar carcinoma, pulmonary siderosis, and hematogenous metastases from primary cancers of thyroid, kidney, trophoblast, and some of the sarcomas.1,2 Primary lung cancer with hematogenous spread may cause miliary shadows. Although nonspecific, this radiographic finding may be helpful in certain clinical scenarios. In our case, diagnosing TB is tempting, but tissue diagnosis is essential for accurate management.

Pulmonary Histopathology in Dalmatians with Familial Acute Respiratory Distress Syndrome (ARDS)

The histopathological changes in the lungs of 12 related Dalmatians with idiopathic acute respiratory distress syndrome (ARDS) are described. Affected dogs had multiple foci of marked atypical hyperplasia and squamous metaplasia of the bronchiolar epithelium, patchy ongoing fibrosis with myofibroblastic metaplasia, smooth muscle hyperplasia and occasional honeycombing of alveolar walls, and hyperplasia of atypical type II pneumocytes. There was an abrupt transition between these proliferative lesions and areas of acute alveolar oedema with hyaline membranes in partially normal lung. Diseased areas were associated with moderate lymphohistiocytic interstitial inflammation. Immunohistochemical labelling for cytokeratin expression indicated that the metaplastic epithelium was of bronchiolar origin and that it extended into peribronchiolar alveolar spaces. Some of the bronchiolar lesions were pre-neoplastic and one adult dog suffered from bronchoalveolar carcinoma. These lesions are compared with the two forms of idiopathic interstitial pneumonia reported as causes of ARDS in man: acute interstitial pneumonia (AIP) and acute exacerbation of idiopathic pulmonary fibrosis (IPF). The observed lesions in the Dalmatians are distinct from the diffuse alveolar damage that characterizes AIP, but show some histological similarities to the usual interstitial pneumonia (UIP) that occurs in IPF with acute exacerbation in man. UIP has not previously been described in the dog.

P23: Whole slide image analysis with smart tissue finding on common toxicological problems

Whole slide imaging offers the ability to observe and quantitate areas of interest on much larger sample sizes, including an entire tissue sample. Quantitation is typically either morphologic (e.g. cellular hypertrophy or tissue infiltrates) or biomarker expression with special stains (e.g. in-situ hybridization or immunohistochemistry). Quantitation requires that a pathologist either draw a region of interest or provide highly specific tissue staining prior to the computer calculating the results. This step can be particularly challenging in cases with large and morphologically intricate areas of tissue, or when tissue staining is nonspecific. The pathologist needs to be able to identify regions to include or exclude, and then ask the computer to find all similar regions and classify the tissue. Once this Smart Tissue Finding step has been completed, the pathologist can then run quantitative image analysis on the regions found by the computer across the entire slide. The Smart Tissue Finding algorithm Genie (GENetic Imagery Exploitation) from Los Alamos National Laboratory was used in conjunction with Aperio quantitation algorithms to access the ability of a pathologist to train the computer to find different tissue types or histopathology common in toxicology and other studies. The following four examples are demonstrated: human bronchoalveolar carcinoma, mouse spleen, rat liver with necrosis and rat liver with biliary hyperplasia and peribiliary lymphoid infiltrates. It was found that lesions and tissues of interest could be consistently distinguished by Smart Tissue Finding in the above examples evaluated.

Surgical Resection Is Justified in Non-Small Cell Lung Cancer Patients with Node Negative T4 Satellite Lesions

The management of non-small cell lung cancer (NSCLC) depends on the stage, with a satellite nodule in the same lobe being classified as T4 stage IIIB even in node negative patients. Controversy exists as to the optimal management of these patients. Our objectives were to evaluate the outcomes in surgically resected patients with a T4 satellite lesion and to analyze the prognostic factors associated with outcome. Patients who underwent resection for T4 (satellite nodule) N0-2M0 were identified. Patients with pure bronchoalveolar carcinoma were excluded. The primary endpoint studied was overall survival. Multiple covariates were analyzed for association with survival and recurrence. A total of 51 T4 N0-2 patients (men 22, women 29; median age 71 years [48 to 87]) underwent resection over a 7-year period. At a median follow-up of 26.4 months the estimated 5-year overall survival was 26% (95% confidence interval [CI] 14% to 50%; median survival 25.2 months). The estimated 5-year overall survival for T4 N0 patients was 40% (95% CI 23% to 68%; median survival 34.8 months). Size of the primary tumor, histology, and nodal status were significantly associated with overall survival; size and nodal status were significantly associated with disease-free survival. Our results indicate that T4 (satellite nodule) N0 patients experienced excellent survival after surgical resection. These data support surgical resection in node negative patients. Size, histology, and nodal status were important prognostic variables associated with outcome. Consideration should be given to multimodality treatment in patients with adverse prognostic features. Further larger multiinstitutional studies are required to validate these findings.

The Growth and Tumor Suppressors NORE1A and RASSF1A Are Targets for Calpain-Mediated Proteolysis

BackgroundNORE1A and RASSF1A are growth and tumour suppressors inactivated in a variety of cancers. Methylation of NORE1A and RASSF1A promoters is the predominant mechanism for downregulation of these proteins; however, other mechanisms are likely to exist.Methodology/Principal FindingsHere we describe a proteolysis of NORE1A and RASSF1A by calpains as alternative mechanism of their downregulation. Extracts of H358 cell line, a human bronchoalveolar carcinoma, and H460, a large cell carcinoma, were capable of proteolysis of NORE1A protein in the calpain-dependent manner. Likewise, RASSF1A tumor suppressor was proteolyzed by the H358 cell extract. Addition of calpain inhibitor to H358 and H460 cells growing in tissue culture resulted in re-expression of endogenous NORE1A. A survey of 10 human lung tumours revealed that three of them contain an activity capable of inducing NORE1A degradation.Conclusions/SignificanceThus, degradation by calpains is a novel mechanism for downregulation of NORE1A and RASSF1A proteins and might be the mechanism allowing cancer cells to escape growth suppression.

Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

Purpose To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first ( n = 4), followed by osteosarcoma ( n = 2), fusiform cell sarcoma ( n = 1), undifferentiated sarcoma ( n = 1), neurosarcoma ( n = 1) and myxoid sarcoma ( n = 1). Other histological types of malignant transformation included adenocarcinoma ( n = 3) and bronchoalveolar carcinoma ( n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60–168). Results Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3–180), 4 out of 14 patients were alive. Conclusion TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful as CT and MR findings may suggest this entity and lead to an early biopsy and appropriate treatment.

Dyspnea on Exertion and Ground-Glass Infiltrates in an Ex-Smoker

Dyspnea on Exertion and Ground-Glass Infiltrates in an Ex-Smoker

Monoclonal antibody 14C5 targets integrin αvβ5

This study identifies and characterizes the antigen recognized by monoclonal antibody (mAb) 14C5. We compared the expression of antigen 14C5 with the expression of eight integrin subunits (alpha1, alpha2, alpha3, alphav, beta1, beta2, beta3, and beta4) and three integrin heterodimers (alphavbeta3, alphavbeta5, and alpha5beta1) by flow cytometry. Antigen 14C5 showed a similar expression to alphavbeta5 in eight different epithelial cancer cell lines (A549, A2058, C32, Capan-2, Colo16, HT-1080, HT-29, and SKBR-3). Specific binding of P1F6, an anti-alphavbeta5 specific antibody, was blocked by mAb 14C5. After transient expression of alphavbeta5 in 14C5-negative Colo16 cells, mAb 14C5 was able to bind a subpopulation of alphavbeta5-positive cells. We evaluated the tissue distribution of the 14C5 antigen in colon (n = 20) and lung (n = 16) cancer tissues. The colon carcinoma cells stained positive for 14C5 in 50% of tumors analyzed, whereas bronchoalveolar lung carcinoma and typical carcinoid were not positive for the antigen. More common types of non-small cell lung cancer, i.e., squamous (n = 5) and adenocarcinoma (n = 3), stained positive in 2 of 5 squamous carcinomas and in 1 of 3 investigated adenocarcinoma. Colon (95%) and lung (50%) carcinoma tissues showed extensive expression of antigen 14C5 in the stroma surrounding the tumor cells and on the membrane of the adjacent fibroblasts. We show for the first time that mAb 14C5 binds the vascular integrin alphavbeta5, suggesting that mAb 14C5 can be used as a screening agent to select colon and lung cancer patients that are eligible for anti-alphavbeta5-based therapies.

Down-regulation of Micro-RNA-1 (miR-1) in Lung Cancer: Suppression of Tumorigenic Property of Lung Cancer Cells and Their Sensitization to Doxorubicin-Induced Apoptosis by miR-1

Micro-RNAs are approximately 21-25-nucleotide-long noncoding RNAs that regulate gene expression primarily at the post-transcriptional level in animals. Here, we report that micro-RNA-1 (miR-1), abundant in the cardiac and smooth muscles, is expressed in the lung and is down-regulated in human primary lung cancer tissues and cell lines. In situ hybridization demonstrated localization of miR-1 in bronchial epithelial cells. The tumor suppressor C/EBPalpha, frequently suppressed in lung cancer, reactivated miR-1 expression in the lung cancer cells. Repressed miR-1 was also activated in lung cancer cells upon treatment with a histone deacetylase inhibitor. These observations led us to examine the antitumorigenic potential of miR-1 in lung cancer cells. Expression of miR-1 in nonexpressing A549 and H1299 cells reversed their tumorigenic properties, such as growth, replication potential, motility/migration, clonogenic survival, and tumor formation in nude mice. Exogenous miR-1 significantly reduced expression of oncogenic targets, such as MET, a receptor tyrosine kinase, and Pim-1, a Ser/Thr kinase, frequently up-regulated in lung cancer. Similarly, the levels of two additional targets, FoxP1, a transcription factor with oncogeneic property, and HDAC4 that represses differentiation-promoting genes, were reduced in miR-1-expressing cells. Conversely, depletion of miR-1 facilitated N417 cell growth with concomitant elevation of these targets. Further, ectopic miR-1 induced apoptosis in A549 cells in response to the potent anticancer drug doxorubicin. Enhanced activation of caspases 3 and 7, cleavage of their substrate PARP-1, and depletion of anti-apoptotic Mcl-1 contributed to the sensitivity of miR-1-expressing cells to doxorubicin. Thus, miR-1 has potential therapeutic application against lung cancers.

Erlotinib after Failure of Gefitinib in Patients with Advanced Non-small Cell Lung Cancer Previously Responding to Gefitinib

Gefitinib and erlotinib are two orally active epidermal growth factor receptor tyrosine kinase inhibitors used in the treatment of advanced non-small cell lung cancer (NSCLC). Gefitinib was the first one to become available in Europe in an expanded access program. When erlotinib granted approval, there were many patients who had progressed after receiving gefitinib and different lines of chemotherapy with no further treatment options; moreover, the results of clinical trials suggested possible significant differences in the mechanisms of sensitivity and in the efficacy between these two agents. Advanced NSCLC White patients, previously treated with almost two lines of chemotherapy and with gefitinib, obtaining a partial response or a stable disease with this agent, were treated with erlotinib after progression of disease to gefitinib. Only eight patients resulted eligible because of the unavailability of gefitinib after the closure of the expanded access program. Four patients were women; histologic diagnosis was adenocarcinoma in four cases and bronchoalveolar carcinoma or unspecified NSCLC in two cases each. Median age was 70 years (range, 53-85). Seven out of eight patients had never smoked, one was a former smoker.We obtained two partial responses and three stable diseases with erlotinib with a median duration of response of 8 months. The median time to progression and overall survival were 5.9 and 14.6 months, respectively. Erlotinib seems to be a potential therapeutic option for treatment of selected advanced NSCLC patients after failure of gefitinib. Further studies are warranted to evaluate the molecular mechanisms behind this evidence and clarify how to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

Sublobar resection in nonsmall cell lung carcinoma

Though lobectomy remains the standard of care for resection of nonsmall cell lung cancer, a number of studies have been published in the last 24 months exploring the role of sublobar resection in the treatment of stage I nonsmall cell lung cancer. Large retrospective studies comparing lobar and sublobar resection show similar overall and disease-free survival. Survival and local control for sublobar resections are best for tumors smaller than 2 cm and with margins greater than 2 cm. Importantly, sublobar resections commonly have less thorough nodal dissection and incomplete pathologic staging; this may have important therapeutic consequences. No formal comparison of segmentectomy to wedge resection has been performed although bias towards segmentectomy resulting in better outcomes than nonanatomic wedge resection continues. Sublobar resection is especially interesting for patients with prior resection, bronchoalveolar carcinoma, and the elderly. Radiologic criteria for selecting candidates appropriate for sublobar resection are evolving. Sublobar resection is an alternative therapy for stage I nonsmall cell lung cancer for patients with physiologic impairment unable to undergo lobectomy. The literature also suggests a role for patients with prior lung resection, bronchoalveolar carcinoma, peripheral tumors less than 2 cm, and for the elderly.

Gemcitabine and oxaliplatin (GEMOX), a promissing combination for the treatment of relapsed, advanced or metastatic non small cell lung cancer (NSCLC)

19061 Background: Combination of Gemcitabine and Oxaliplatin (GEMOX) given every 3 weeks was reported to be safe and active in phase II studies in first and second line therapy of NSCLC. The aim of our trial was to assess the efficacy and safety of oxaliplatin in combination with fixed rate infusion gemcitabine in the second and third line treatment of NSCLC, and to assess quality of life (QOL). Methods: 30 patients with advanced NSCLC, with Performance status (PS) ECOG 0–1, and who had failed first or second line treatment with chemotherapy and/or tyrosine kinase inhibitors were treated with GEM 1,000 mg/m2 over 100 min in combination with O× 100 mg/m2 over 2 hours both given on days 1 and 15 of each 28-day cycle. Primary endpoint was ORR and secondary endpoints were toxicity, time to tumor progression, time to treatment failure, overall survival. QOL was assessed by the FACT-L V.4 and Lung Cancer Subscale (LCS) questionnaires. Results: From the 30 patients, 16 (53%) were males and 14 (47%) females. 20 patients were Hispanics (66%), 7 Caucasian (23%), 3 African American (10%). Median age was 56 years. PS was ECOG 0 and 1 in 14(47%) and 16(53%) respectively. Histological subtypes were adenocarcinoma in 14 patients (47%), adeno-squamos in 1(3%), squamos in 3(1%), Bronchoalveolar carcinoma in 2 (6%) and unspecified in 9 (30%) patients. The treatment was second line for 22 (73%) patients and third line for 7(23%) patients. 1 patient progressed quickly and became ineligible for the treatment after enrollment. Two patients died on study from disease progression leading to respiratory and multi-organ failure. Partial responses were achieved in 4 (13%) patients, stable disease in 12 (40%) and progressive disease in 12 (40%). Grade 3/4 adverse events were seen in <10% of the patients and included fatigue, dyspnea, anemia and multiorgan failure (1 patient). There was a 25% improvement in the QOL LCS score. Conclusion: GEMOX combination given in day 1 and 15 of every 4 weeks shows activity and tolerable side effects when used to treat patients with advanced NSCLC who have previously failed chemotherapy, tirosine kinase or angiogenesis inhibitors, with a suggestion of QOL improvement. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology, sanofi-aventis sanofi-aventis