A phase II study of paclitaxel in advanced bronchioloalveolar carcinoma (EORTC trial 08956)

Scagliotti, G.; Smit, Egbert F.; Bosquee, Léon; O’Brien, Michelle; Ardizzoni, Andrea; Zatloukal, Petr; Eberhardt, Wilfried; Smid-Geirnaerdt, M.J.A.; Bruin, Hein G. de; Dussenne, S.; Legrand, Catherine; Giaccone, Giuseppe

doi:10.1016/j.lungcan.2005.05.012

Cited by 42 publications

(19 citation statements)

References 20 publications

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“…Our DCR and PFS results were similar to those previously reported in an advanced BAC population [4,5,[7][8][9][10][11]. DCR did not differ between therapeutic arms or pathological subtypes, although there was a strong interaction between treatment effect (arm E versus CP) on PFS and mucinous and NM subtypes (p=0.009) (figure 3), as previous studies have suggested [10].…”

Section: Discussionsupporting

confidence: 90%

“…Only two nonrandomised phase II trials had previously investigated the efficacy of paclitaxel monotherapy, administered every 3 weeks [4,5], but the low response rates and unacceptable toxicity reported by the Southwest Oncology Group (SWOG) 9714 trial defined this approach as ill adapted [5]. Pemetrexed monotherapy has recently achieved promising results in the Intergroupe Francophone de Cancérologie Thoracique (French Cooperative Thoracic Intergroup (IFCT)) 0401 trial [6] and in one prematurely closed phase II trial [7].…”

Section: Introductionmentioning

confidence: 99%

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Erlotinibversuscarboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504

Cadranel¹,

Gervais²,

Merle³

et al. 2015

Eur Respir J

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The IFCT-0504 phase II trial evaluated the efficacy of erlotinib versus carboplatin-paclitaxel (CP) as first-line treatment in 130 cases of advanced lepidic-predominant adenocarcinoma (ADC).The primary objective of the study was treatment efficacy, evaluated based on an end-point of disease control at 16 weeks.The primary objective was met, with a disease control in 35 (53%) out of 66 patients treated with CP and in 25 (39.1%) out of 64 patients treated with erlotinib. Median progression-free survival (PFS) for the total population was 3.6 months. The disease control rate did not differ between either the therapeutic arms or pathological subtypes, whereas there was a strong interaction between treatment arms and tumour pathological subtypes for PFS ( p=0.009). Mucinous tumour patients treated with erlotinib exhibited an increased progression risk (hazard ratio 3.4, 95% CI 1.7-6.5; p⩽0.001). The PFS for nonmucinous tumour patients was similar in both arms. Median overall survival was 20.1 months and did not differ between therapeutic arms. These findings were not further elucidated by molecular analyses and the toxicity profiles were as expected.Our study demonstrated the dominant role of CP alongside erlotinib in the management of advanced lepidic ADC. Based on these findings, erlotinib should not be administered in first-line therapy to patients with lepidic ADC in the absence of an epidermal growth factor receptor mutation. @ERSpublications Interaction between pathological subtypes and treatment (erlotinib/chemotherapy) in advanced lepidic adenocarcinoma

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Erlotinibversuscarboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504

Cadranel¹,

Gervais²,

Merle³

et al. 2015

Eur Respir J

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“…In 1999, the World Health Organization updated its classification and redefined bronchioloalveolar carcinoma (BAC) as being restricted to noninvasive tumors. Since this reclassification, prognostic features of patients with newly defined BAC have not been well defined, in spite of the fact that the disease appears to have a distinct clinical course and response to treatment (2,3). Although typically resistant to traditional chemotherapies, BAC is highly sensitive to EGFR-TKIs such as erlotinib and gefitinib.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma

et al. 2007

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Purpose: Lung cancer is the leading cause of cancer related mortality in the world. BAC is a subset of NSCLC that has recently gained attention because of distinct biologic and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC.Methods: 46 cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously.Results: Age and histology (mucinous vs. non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95% CI 1.07-4.71, p=0.032), advanced stage (III or IV) (HR 2.17, p=0.049), and smoking status (HR 6.89, 95% CI 1.49-31.88, p=0.013) were associated with a worse prognosis. Conclusions:Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients.

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“…Median survival was 8.6 months and 1-year survival was 35.0% (95% CI 14.1-55.8). Paclitaxel was manageable but with limited efficacy [53].…”

Section: Chemotherapymentioning

confidence: 99%

Targeted therapies in bronchioloalveolar carcinoma

Scagliotti

Selvaggi

2008

Targ Oncol

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Bronchioloalveolar carcinoma (BAC) is a subtype of adenocarcinoma with unique epidemiology, pathology, clinical features, radiographic presentation, and natural history compared with other non-small cell lung cancer (NSCLC) subtypes. According to criteria of the revised 2004 World Health Organization classification it accounts for only 5% of all cases of NSCLC. BAC cases are mostly represented by females and non-smokers and are diagnosed at a younger age. Patients with resected BAC have prolonged survival and a lower recurrence rate after surgical resection than other NSCLC subtypes. In advanced BAC cytotoxic chemotherapy seems as effective as in other NSCLC, although studies on pure BAC are based on small numbers of patients and mainly tested paclitaxel based regimens on preclinical activity on cell lines. A higher than expected response rate to the epidermal growth factor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib was recorded in BAC or in adenocarcinomas with BAC features compared with other NSCLC subtypes, mainly due to a higher rate of neversmoking patients. In fact, these agents demonstrated activity in the first-line setting especially in patients harboring EGFR mutations. The role of molecular predictors of response and survival such as EGFR gene amplification or EGFR mutations is an open field of research in fine-tuning BAC management. New drugs are being tested in advanced BAC, while more prospective data must be collected on predictive and prognostic factors.

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A phase II study of paclitaxel in advanced bronchioloalveolar carcinoma (EORTC trial 08956)

Cited by 42 publications

References 20 publications

Erlotinibversuscarboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504

Erlotinibversuscarboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504

Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma

Targeted therapies in bronchioloalveolar carcinoma

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