Phase II trial of oral topotecan and intravenous carboplatin with G-CSF support in previously Untreated Patients With Extensive Stage Small Cell Lung Cancer: A north central cancer treatment group study

Alan H Bryce, Bassam Mattar, Shauna L. Hillman, Alex Adjei, John W. Kugler, Kendrith Rowland, Donald B. Wender, Gamini Soori, Edith A. Perez, James R. Jett

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)353-357
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume33
Issue number4
DOIs
StatePublished - Aug 2010

Fingerprint

Topotecan
Carboplatin
Small Cell Lung Carcinoma
Granulocyte Colony-Stimulating Factor
Neoplasms
Therapeutics
Topoisomerase I Inhibitors
Survival
Sudden Cardiac Death
Platinum
Dyspnea
Hypotension
Area Under Curve
Vomiting
Diarrhea
Intercellular Signaling Peptides and Proteins
Infection
Pharmaceutical Preparations

Keywords

  • Filgastrim
  • Phase II
  • Small cell lung cancer
  • Topotecan

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

Phase II trial of oral topotecan and intravenous carboplatin with G-CSF support in previously Untreated Patients With Extensive Stage Small Cell Lung Cancer : A north central cancer treatment group study. / Bryce, Alan H; Mattar, Bassam; Hillman, Shauna L.; Adjei, Alex; Kugler, John W.; Rowland, Kendrith; Wender, Donald B.; Soori, Gamini; Perez, Edith A.; Jett, James R.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 33, No. 4, 08.2010, p. 353-357.

Research output: Contribution to journalArticle

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abstract = "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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AU - Bryce, Alan H

AU - Mattar, Bassam

AU - Hillman, Shauna L.

AU - Adjei, Alex

AU - Kugler, John W.

AU - Rowland, Kendrith

AU - Wender, Donald B.

AU - Soori, Gamini

AU - Perez, Edith A.

AU - Jett, James R.

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