Phase III Double-Blind, Placebo-Controlled Study of Thalidomide in Extensive-Disease Small-Cell Lung Cancer After Response to Chemotherapy: An Intergroup Study FNCLCC cleo04–IFCT 00-01

Small cell lung cancer (SCLC) is an aggressive lung tumour strongly associated with cigarette smoking, with patients often presenting with metastatic disease at the time of diagnosis. Although SCLC is very chemoradiosensitive and high response rates are obtained with treatment, relapse rates are high and the prognosis remains very poor.In limited-stage SCLC, the overall survival rate has been significantly improved by adding dosehyperfractionated thoracic radiotherapy and prophylactic cranial irradiation to systemic chemotherapy. In contrast, little progress has been made in the treatment of extensive-stage SCLC (ES-SCLC), apart from the recently documented survival gain by the addition of prophylactic cranial irradiation.First-line therapy in ES-SCLC currently consists of chemotherapy, combining a platinum drug with either etoposide or irinotecan as a possible alternative.New treatments are needed in order to improve the prognosis of ES-SCLC, as median survival with current standard treatment is still only 9-10 months from diagnosis. The present review focuses on the management of ES-SCLC, with special attention to the development of new treatment options.KEYWORDS: Chemotherapy, extensive disease, radiotherapy, small cell lung cancer, treatment S mall cell lung cancer (SCLC) is an aggressive malignant disease, with the majority of patients presenting with distant metastasis at diagnosis. A separate staging system has been developed for SCLC, classifying SCLC as limited or extensive disease [1]. The International Association for the Study of Lung Cancer defines limited-stage SCLC (LS-SCLC) as: ''disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and ipsilateral and contralateral supraclavicular nodes and should also include patients with ipsilateral pleural effusion independent of whether cytology is positive or negative '' [2]. Patients with SCLC who do not fit this definition are considered to have extensive-stage SCLC (ES-SCLC). This staging system was used to select the appropriate treatment regimen: chemotherapy in combination with thoracic radiotherapy in patients with LS-SCLC, and chemotherapy alone in patients with ES-SCLC. Recent data suggest that the tumour, node, metastasis classification traditionally reserved for the staging of nonsmall cell lung cancer (NSCLC) can also be applied for the staging of SCLC [3].

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“…However, two large randomised phase III trials failed to show a significant benefit of thalidomide in the treatment of SCLC [106,113].…”

Section: Targeted Therapiesmentioning

confidence: 99%

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Demedts

Vermaelen²,

Meerbeeck³

2009

Eur Respir J

185

162

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“…In a phase III study, which was stopped early due to poor accrual, 92 ES SCLC patients with chemotherapy responsive disease were randomized to receive cisplatin, etoposide, epirubicin and cyclophosphamide, with or without thalidomide. Despite the small size of the study, a statistically significant difference in survival was observed in favor of the thalidomide arm: 11.7 versus 8.7 months (hazard ratio: 0.48; 95% confidence interval: 0.24-0.93; p = 0.03) [44]. More patients on the thalidomide treatment arm withdrew from the study due to toxicity (33% versus 19%), notably neuropathy and constipation.…”

Section: Basic Fibroblast Growth Factormentioning

confidence: 83%

Fast, hungry and unstable: finding the Achilles’ heel of small-cell lung cancer

Hann

Rudin

2007

Trends in Molecular Medicine

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Over 95% of patients with small-cell lung cancer (SCLC) die within five years of diagnosis. The standard of care and the dismal prognosis for this disease have not changed significantly over the past 25 years. Some of the characteristics of SCLC that have defined it as a particularly virulent form of cancer -rapid proliferation, excessive metabolic and angiogenic dependence, apoptotic imbalance and genetic instability -are now being pursued as tumor-specific targets for intervention both in preclinical and early phase clinical studies. Here, we summarize areas of ongoing anti-cancer drug development, including classes of agents that target essential pathways regulating proliferation, angiogenesis, apoptotic resistance, chromosomal and protein stability, and cell-cell and cell-matrix interaction.

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“…In a French phase III randomized controlled trial by Pujol et al (56), 119 patients with ED-SCLC were treated with 2 cycles of PCDE (cisplatin/cyclophosphamide/ epidoxorubicin/etoposide). Those who achieved an objective response (97 patients) were randomly assigned to receive 4 additional cycles of PCDE plus oral thalidomide 400 mg/d or placebo.…”

Section: Thalidomidementioning

confidence: 99%

Targeting angiogenesis in small cell lung cancer

Stratigos

Matikas

Voutsina

et al. 2016

Transl. Lung Cancer Res.

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Small cell lung cancer (SCLC) is a highly aggressive and lethal malignancy. Despite high initial response rates to systemic chemotherapy, the disease eventually relapses; further treatment only modestly improves outcomes and overall survival (OS) for patients with extensive stage disease is less than one year.Little progress has been made during the past decades, with no new drugs approved. Consequently, the development of novel strategies is an unmet need. The inhibition of angiogenesis, a defining characteristic of cancer, has demonstrated modest efficacy in several human malignancies, including non-small cell lung cancer (NSCLC). However, results from clinical trials in SCLC have been disappointing, and no anti-angiogenic agent has received regulatory approval due to lack of clinical efficacy. The elucidation of underlying mechanisms responsible for tumor resistance to angiogenic therapy and the simultaneous blockade of multiple elements that play a role in angiogenesis need to be further explored.

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Phase III Double-Blind, Placebo-Controlled Study of Thalidomide in Extensive-Disease Small-Cell Lung Cancer After Response to Chemotherapy: An Intergroup Study FNCLCC cleo04–IFCT 00-01

Cited by 133 publications

References 26 publications

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Fast, hungry and unstable: finding the Achilles’ heel of small-cell lung cancer

Targeting angiogenesis in small cell lung cancer

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