Phase II Trial of Paclitaxel and Carboplatin in Metastatic Small-Cell Lung Cancer: A Groupe Français de Pneumo-Cancérologie Study

Thomas, P.; Castelnau, Olivier; Paillotin, D.; Léna, H.; Robinet, G.; Muir, Jean-François; Delaval, P.; Gouva, S.; Balmès, P; Blanchon, F; Perdu, D.; Poirier, R; Santi, P Pommier de; Penot-Ragon, Christine; Kleisbauer, J P

doi:10.1200/jco.2001.19.5.1320

Cited by 38 publications

(16 citation statements)

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“…As a single agent, paclitaxel has a response rate in the 30–50% range in chemotherapy naïve patients with SCLC (24–26). When the drug was combined with platinum agents (carboplatin and cisplatin), the overall response rates (ORRs) were 65–68% (27,28). While this ORR is comparable to the ‘gold standard’ regimen of cisplatin or carboplatin plus etoposide, the complete response (CR) rates were lower, with only ~5–10% achieving a CR with platinum plus paclitaxel versus ~20–40% achieving a CR with platinum plus etoposide (29,30).…”

Section: Discussionmentioning

confidence: 99%

High expression of class III β-tubulin in small cell lung carcinoma

et al. 2013

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Class III β-tubulin (TUBB3) is emerging as a biomarker in a number of cancers. TUBB3 has been shown to be a prognostic indicator of more aggressive disease and a predictor of resistance to taxanes and vinca alkaloids. To date, there is little data on TUBB3 expression in small cell lung carcinoma (SCLC). The primary objective of this study was to determine the expression of TUBB3 in SCLC. Immunohistochemical staining of SCLC tumor specimens was performed using standard procedures. Expression of TUBB3 was determined as a composite of the percentage of malignant cells staining positive and the intensity of staining. Clinical and tumor data for each patient was compared with the degree of TUBB3 expression. A total of 66 SCLCs were evaluable for TUBB3 expression. The majority of specimens (n=56, 85%) had high expression of TUBB3. Only 4.5% (n=3) had low expression of TUBB3. The mean distribution of positive staining for the specimens was 87.3±1.8% (mean ± SE). Specimens from core biopsies were significantly more likely to have high TUBB3 expression when compared with fine needle aspirates (P=0.004). There were no other significant findings when comparing clinical or tumor characteristics. Overall, we found that expression of TUBB3 in SCLC is higher than expected. Innate resistance to microtubule inhibitors, such as the taxanes and vinca alkaloids, may be associated with this finding. Attempts at microtubule inhibition with novel agents may be able to overcome this resistance mechanism. Further evaluation of TUBB3 as a biomarker in SCLC is warranted.

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Section: Discussionmentioning

confidence: 99%

High expression of class III β-tubulin in small cell lung carcinoma

et al. 2013

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“…The study actually enrolled 38 patients in three years and it was decided to halt the trial because of the highly positive experience with this concurrent chemo-radiotherapy. This decision was also weighed by data from other studies (Kirschling et al, 1999;Thomas et al, 2001). Survival was analysed using a Kaplan Meier curve.…”

Section: Discussionmentioning

confidence: 99%

Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study

Baas

Belderbos

Senan³

et al. 2006

Br J Cancer

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To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the addition of concurrent thoracic radiotherapy to a platinum-containing regimen is important. In the Netherlands, we initiated a multicenter, phase II study, of the combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m À2) and etoposide (2 Â 50 mg orally for 5 days) combined with 45 Gy (daily fractions of 1.8 Gy). The radiation was given to the involved field and concurrently with the second and third chemotherapy cycle. Patients with a partial or complete response received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999 to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in 57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment-related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%) and lethargy (22%). The objective response rate was 92% (95% confidence interval (CI) 80 -98%) with a median survival time of 19.5 months (95% CI 12.8 -29.2). The 1-, 2-and 5-year survival rate was 70, 47 and 27%, respectively. In field local recurrences occurred in six patients. Distant metastases were observed in 19 patients of which 13 in the brain. This study indicates that combination chemotherapy with concurrent involved-field radiation therapy is an effective treatment for LS-SCLC. Despite PCI, the brain remained the most important site of recurrence.

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“…The rationale for combining ipilimumab with chemotherapy was based on preclinical and clinical findings suggesting that certain chemotherapeutic agents augment the activity of ipilimumab [35,36]. Although paclitaxel plus carboplatin is not a traditional regimen for SCLC, it was chosen as the comparator because it is a standard regimen for NSCLC patients and because data show benefits with this combination in SCLC [37,38]. Treatment administration was concurrent (ipilimumab plus paclitaxel and carboplatin for four cycles followed by placebo plus paclitaxel and carboplatin for two cycles; n 5 43) or phased (placebo plus paclitaxel and carboplatin for two cycles followed by ipilimumab plus paclitaxel and carboplatin for four cycles; n 5 42), with a control group receiving only placebo plus paclitaxel and carboplatin for the same total number of doses (n 5 45) [34].…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

The Future of Immunotherapy in the Treatment of Small Cell Lung Cancer

2016

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Small cell lung cancer (SCLC), which accounts for 10%-15% of lung cancer cases, is an aggressive disease characterized by rapid growth and early widespread metastasis. Although up to 80% of patients respond to first-line chemotherapy, most eventually relapse, and there are no approved agents beyond the second line. Despite the high incidence of mutations in SCLC, to date no targeted therapy has shown a benefit for this patient population, and systemic treatment has not changed significantly during the past 3 decades. Given that extensive-stage SCLC has a 5-year survival rate of only 1%-2%, novel therapies are desperately needed. Recent evidence shows that the immune system is capable of generating antitumor responses against various tumors, including lung cancer, suggesting that immunotherapy may be a viable therapeutic approach to the treatment of patients with SCLC. Of the immunotherapies being investigated for patients with SCLC, antibodies that target the programmed cell death protein-1 (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte antigen-4 (ipilimumab) immune checkpoint pathways are perhaps the most promising. Because these immune checkpoint pathways, which under normal circumstances function to protect healthy tissues from damage during inflammatory responses and maintain self-tolerance, can help tumor cells evade elimination by the immune system, they represent potential therapeutic targets.This review discusses the rationale for immunotherapy and the early clinical results of immunotherapeutic agents being investigated in SCLC. The Oncologist 2016;21:910-921 Implications for Practice: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype. Despite sensitivity to first-line chemotherapy, SCLC has high recurrence rates, and responses to second-line treatments are poor. Recent evidence shows that the immune system is capable of generating responses against various tumors, including lung cancer, suggesting that immunotherapy may be a viable approach for patients with SCLC. Of several immunotherapies being investigated, antibodies that target the programmed cell death protein-1 (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte antigen-4 (ipilimumab) immune checkpoint pathways are among the most promising for patients with SCLC and are the focus of this review.

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Phase II Trial of Paclitaxel and Carboplatin in Metastatic Small-Cell Lung Cancer: A Groupe Français de Pneumo-Cancérologie Study

Abstract: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.

Cited by 38 publications

References 11 publications

High expression of class III β-tubulin in small cell lung carcinoma

High expression of class III β-tubulin in small cell lung carcinoma

Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study

The Future of Immunotherapy in the Treatment of Small Cell Lung Cancer

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