Chemotherapy versus best supportive care for extensive small cell lung cancer

Alvarez, Marta Pelayo; Rubio, Oscar Gallego; Cosp, Xavier Bonfill; Varela, Yolanda Agra

doi:10.1002/14651858.cd001990.pub2

Cited by 24 publications

(13 citation statements)

References 70 publications

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“…These data suggest that clinical trial results are a strong driver of the adoption of new therapies in the real world. Various other agents used for the treatment of SCLC, especially in the salvage setting, were adopted on the basis of limited evidence generally adduced from small phase 2 studies . The demonstration in this study that agents such as paclitaxel, docetaxel, and gemcitabine confer a survival advantage in the real world is, therefore, important and provides additional support for this strategy, which is part of current treatment guidelines.…”

Section: Discussionmentioning

confidence: 99%

Trends, predictors, and impact of systemic chemotherapy in small cell lung cancer patients between 1985 and 2005

Behera

Ragin

Kim

et al. 2015

Cancer

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Background The last three decades have witnessed limited therapeutic advances in SCLC management. We evaluated real-world trends in use of systemic therapies and the impact on patient outcome in US. Methods We employed SEER-MEDICARE for SCLC patients diagnosed between 1985 and 2005. The 1985-1990 period served as baseline for temporal analysis conducted at 5-year intervals (1985-1990, 1991-1995, 1996-2000, 2001-2005). Cox proportional models were employed to estimate the effect of chemotherapy on survival. Results were validated using propensity-matched analysis. Results There were 47,351 eligible patients; male (52%); median age: 71 years; Whites-87%; Blacks-7%; Asians-1.4%. The proportion of patients treated with chemotherapy was low but increased over time (38, 55, 50, 53%; p<0.001). Race, diagnosis period, age, stage and location of residence significantly predicted chemotherapy use. Females (51%), Asians (53%) and rural residents (60%) were more likely to receive chemotherapy. The median overall survival with and without chemotherapy was 9.6 and 3.6 months. Linear trend analyses showed modest reduction in the impact of chemotherapy on survival in patients treated with chemotherapy over untreated patients (HRs: 0.59, 0.61, 0.64, 0.62; p<0.001) but an overall trend of improved survival within treated (HRs: 1.0, 1.03, 1.00, 0.96; p=0.005) and untreated (HRs: 0.99, 0.94, 0.92; p<0.001) patients. There was no survival difference between patients treated with carboplatin versus cisplatin (HR: 0.99 CI: 0.81-1.19; p=0.875). Additional therapy beyond platinum-based chemotherapy was associated with survival benefit (HR: 0.78 CI: 0.75-0.81; p<0.001). Conclusions Chemotherapy use was associated with survival benefit in MEDICARE SCLC patients treated in the real-world setting.

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Section: Discussionmentioning

confidence: 99%

Trends, predictors, and impact of systemic chemotherapy in small cell lung cancer patients between 1985 and 2005

Behera

Ragin

Kim

et al. 2015

Cancer

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“…Nonetheless, our data indicates that patients with resistant/refractory SCLC derive clinical benefit with the receipt of second line therapy in contrast to historical experience with untreated refractory SCLC where the survival is measured in weeks. 6,38–40 …”

Section: Discussionmentioning

confidence: 99%

A Systematic Analysis of Efficacy of Second-Line Chemotherapy in Sensitive and Refractory Small-Cell Lung Cancer

Owonikoko

Behera

Chen

et al. 2012

Journal of Thoracic Oncology

127

101

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Introduction SCLC patients unresponsive or relapsing within 90 days following frontline chemotherapy have poor prognosis and are treated with regimens different than the first-line regimen. Potential differences in the efficacy of second line therapy for refractory and sensitive SCLC have not been well studied. Methods Studies that enrolled sensitive and refractory (relapse more than or less than 90 days) SCLC patients for second-line therapy were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts databases. A systematic analysis was conducted using Comprehensive Meta Analysis (Version 2.2.048) software to calculate the Odds ratio of response and 95% confidence limits. Median overall survival time for sensitive and resistant SCLC patients was compared by 2-sided Student’s T-Test. We tested for significant heterogeneity by Cochran’s chi-square test and I square index. Results Twenty one studies published between 1984 and 2011 were eligible for this analysis with a total of 1692 patients enrolled; 912 with sensitive and 780 with refractory SCLC. The overall RR was 17.9% with a higher RR of 27.7% (range: 0 – 77%) for sensitive SCLC versus 14.8% (range: 0 – 70%) for refractory patients; p=0.0001. Pooled overall Odds ratio of response was 2.235 (95% CI: 1.518 – 3.291; p=0.001) favoring patients with sensitive disease. Median overall survival time was 6.7 months with a weighted survival of 7.7 and 5.4 months for sensitive and refractory SCLC respectively (p=0.0035). Conclusions Refractory SCLC patients derive modest clinical benefit from second line chemotherapy. However, response and survival outcomes are superior with chemosensitive disease.

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“…Platinum doublets have been preferred more recently because of easier coadministration with radiation therapy in patients with limited disease. SCLC patients are highly sensitive to initial chemotherapy, however, the overall prognosis has improved little over the past two decades, mainly because the response to treatment is often short and the prognosis of relapsed patients who receive second-line therapy, such as topotecan or CAV, is poor 1, 47 . The novel anthracycline amrubicin has been shown to have definite antitumor activity in platinum-refractory SCLC 48 , but randomized studies in second line and in first line have failed to show significant advantages against standard chemotherapy 49 .…”

Section: Discussionmentioning

confidence: 99%

HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small cell lung cancer

et al. 2013

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SCLC at advanced stage is considered an incurable disease. Despite good response to initial chemotherapy, the responses in SCLC patients with metastatic disease are of short duration and resistance inevitably occurs. Although several target-specific drugs have altered the paradigm of treatment for many other cancers, we have yet to witness a revolution of the same magnitude in SCLC treatment. Anthracyclines, such as doxorubicin, have definite activity in this disease, and ganetespib has shown promising activity in preclinical models, but underwhelming activity as a single agent in SCLC patients. Using SCLC cell lines, we demonstrated that ganetespib (IC50: 31nM) was much more potent than 17-AAG, a geldanamycin derivative (IC50: 16 μM). Ganetespib inhibited SCLC cell growth via induction of persistent G2/M arrest and Caspase 3-dependent cell death. MTS assay revealed that ganetespib synergized with both doxorubicin and etoposide, two topoisomerase II inhibitors commonly used in SCLC chemotherapy. Expression of RIP1, a protein that may function as a pro-survival scaffold protein or a pro-death kinase in TNFR1-activated cells, was induced by doxorubicin and downregulated by ganetespib. Depletion of RIP1 by either RIP1 siRNA or ganetespib sensitized doxorubicin-induced cell death, suggesting that RIP1 may promote survival in doxorubicin-treated cells and that ganetespib may synergize with doxorubicin in part through downregulation of RIP1. In comparison to ganetespib or doxorubicin alone, the ganetespib + doxorubicin combination caused significantly more growth regression and death of human SCLC xenografts in immuocompromised mice. We conclude that genetespib and doxorubicin combination exhibits significant synergy and is efficacious in inhibiting SCLC growth in vitro and in mouse xenograft models. Our preclinical study suggests that ganetespib and doxorubicin combination therapy may be an effective strategy for SCLC treatment, which warrants clinical testing.

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Chemotherapy versus best supportive care for extensive small cell lung cancer

Cited by 24 publications

References 70 publications

Trends, predictors, and impact of systemic chemotherapy in small cell lung cancer patients between 1985 and 2005

Trends, predictors, and impact of systemic chemotherapy in small cell lung cancer patients between 1985 and 2005

A Systematic Analysis of Efficacy of Second-Line Chemotherapy in Sensitive and Refractory Small-Cell Lung Cancer

HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small cell lung cancer

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