Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung carcinoma

Hainsworth, John D.; Morrissey, H B S Lisa; Scullin, Daniel C.; Houston, Gerry Ann; Prasthofer, Edgar F.; Gray, James R.; Burris, Howard A.; Greco, F. Anthony

doi:10.1002/cncr.10508

Cited by 24 publications

(9 citation statements)

References 19 publications

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“…18 Similarly, in a trial evaluating the combination of paclitaxel, carboplatin, and topotecan in extensive and limited stage disease, 8% of patients had treatment-related death from sepsis. 19 More specifically, of 12 patients with an ECOG performance status of 2, the treatment-related mortality was 42%. The aforementioned 2006 trial by Hanna et al reported a treatment-related death rate of 5.8%.…”

Section: Discussionmentioning

confidence: 98%

Phase II Trial of Oral Topotecan and Intravenous Carboplatin With G-CSF Support in Previously Untreated Patients With Extensive Stage Small Cell Lung Cancer

Bryce¹,

Mattar²,

Hillman³

et al. 2010

American Journal of Clinical Oncology

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Objectives The objective of this study was to evaluate the response rate and toxicities of the combination of oral topotecan and carboplatin in patients with untreated extensive stage small cell lung cancer (ES-SCLC). Previous studies have suggested improved outcomes with a topoisomerase I inhibitor in combination with a platinum agent. Methods Twenty-six patients with previously untreated, ES-SCLC were evaluable in this phase II trial. All patients received oral topotecan 2.0 mg/m2 per day on days 1 through 5 and carboplatin at an area under curve of 5 on day 5. Treatment was repeated every 21 days up to a total of 6 cycles. All patients received G-CSF. Results There were no complete responses and 16 partial responses, for an overall response rate of 62% (95% CI: 41–80). Median time to progression was 6.0 months (95% CI: 4–8), with a median overall survival of 12 months (95% CI: 8–16). This study was closed to accrual early with 26 of a planned 39 patients enrolled because of grade 5 adverse events in 4 (15%) patients (3 neutropenic infections, 1 sudden cardiac death). Eighty-five percent of patients experienced grade 3 or higher hematologic events. The most common severe nonhematologic events included diarrhea, vomiting, dyspnea, hypoxia, and hypotension. Conclusions Although this drug regimen has activity as first-line therapy in ES-SCLC, it is associated with excessive hematologic toxicity, which occurred in spite of growth factor support. Despite promising survival estimates, this particular combination and dose level of oral topotecan and carboplatin cannot be recommended.

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Section: Discussionmentioning

confidence: 98%

Phase II Trial of Oral Topotecan and Intravenous Carboplatin With G-CSF Support in Previously Untreated Patients With Extensive Stage Small Cell Lung Cancer

Bryce¹,

Mattar²,

Hillman³

et al. 2010

American Journal of Clinical Oncology

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“…Triplet regimens that include ifosfamide, topotecan or paclitaxel have been studied in the frontline setting. 26–30 The paclitaxel, etoposide and carboplatin regimen was compared to carboplatin, etoposide, and vincristine in a phase III clinical trial. The study enrolled a total of 608 evaluable patients and demonstrated reduced risk of death with the addition of paclitaxel (HR 1.22, 95%CI: 1.03–1.45; P =0.024).…”

Section: Management Of Newly Diagnosed Sclcmentioning

confidence: 99%

“…27 Across a large number of randomized trials, the improved efficacy with dose intensification was attained at the cost of increased toxicity and mortality. 26,28,29,31–34 This factor has weighed heavily against widespread adoption of this strategy in the management of SCLC.…”

Section: Management Of Newly Diagnosed Sclcmentioning

confidence: 99%

Small Cell Lung Cancer: Therapies and Targets

Pillai

Owonikoko

2014

Seminars in Oncology

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Small cell lung cancer (SCLC) remains a very fatal disease due to limited therapeutic options. Systemic chemotherapy is the bedrock of treatment for both the limited and extensive stages of the disease. However, the established management paradigm of platinum-based chemotherapy has reached an efficacy plateau. A modest survival improvement, approximately 5%, was witnessed with the addition of cranial or thoracic radiation to systemic chemotherapy. Other strategies to improve outcome of platinum-based chemotherapy in the last 2 decades have met with minimal success. The substitution of irinotecan for etoposide in the frontline treatment of SCLC achieved significant efficacy benefit in Japanese patients but similar benefit could not be reproduced in other patient populations. Salvage treatment for recurrent or progressive SCLC is particularly challenging where topotecan remains the only agent with regulatory approval to date. Ongoing evaluation of biologic agents targeting angiogenesis, sonic hedgehog pathway, DNA repair pathway and immune checkpoint modulators hold some promise for improved outcome in this fatal disease. It is hoped that the coming decade will witness the application of new molecular biology and genomic research techniques to improve our understanding of SCLC biology and identification of molecular subsets that can be targeted appropriately using established and emerging biological agents similar to the accomplishments of the last decade with non small cell lung cancer.

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“…Hainsworth et al [34] /day] on days 1-4 of a 21-day cycle) in patients with extensive SCLC resulted in a more favorable median survival time of 12 months and a 1-year survival rate of 50% [35]. However, five (7%) of the safety-evaluable patients (each with a PS score = 2) died of treatment-related complications.…”

Section: Triplet Regimensmentioning

confidence: 99%

“…The triplet regimen used by Hainsworth et al [34] has also been combined with radiation therapy in patients with limited-stage SCLC [36], where it produced a complete response (CR) rate of 51% and an actuarial median survival time of 20 months. However, severe hematologic toxicities occurred in most patients, hospitalization for febrile or severe neutropenia was required in 11 (14%) patients, and there were three (4%) treatment-related deaths.…”

Section: Triplet Regimensmentioning

confidence: 99%