Phase II trial of edatrexate plus carboplatin in metastatic non-small- cell lung cancer: A Southwest Oncology Group study

D. R. Gandara, Martin J. Edelman, John J. Crowley, Derick H M Lau, Robert B Livingston

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Edatrexate and carboplatin are each active single agents in the treatment of non-small-cell lung cancer (NSCLC). Preclinical studies in NSCLC lines have demonstrated schedule-dependent synergy of edatrexate followed by carboplatin. In a phase I trial, we demonstrated the tolerability of this combination, the ability of ice-chip cryotherapy to ameliorate dose- limiting mucositis, and promising activity in NSCLC. This phase II trial (SWOG 9207) was undertaken to investigate the efficacy of this regimen in stage IV NSCLC. Methods: A total of 24 patients with stage IV disease were accrued to this Southwest Oncology Group (SWOG) multicenter study. Treatment consisted of edatrexate 80 mg/m2 (50% dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m2 every 28 days. Results: Of the 24 patients, 23 were assessable for toxicity and response; one was ineligible for study entry. Myelosuppression was the most significant toxicity; grade 3-4 neutropenia was seen in 8/23 patients. Two patients died of neutropenic sepsis during the first cycle of therapy, in both instances associated with the presence of pleural effusions. Although mild mucositis was common, it was dose-limiting (grade 3) in only three patients. Objective response was observed in 3/23 patients (13%). The median survival time was 7 months, and 30% of patients remained alive at one year. Conclusions: This study suggests that ice-chip cryotherapy is effective in reducing the severity of mucositis typically associated with this edatrexate schedule of administration. However, unexpectedly severe myelosuppression resulted in death from neutropenic sepsis in two patients with third space fluid collections, leading to a protocol amendment to exclude such patients from study entry. Furthermore, response and median survival with this dose schedule of edatrexate and carboplatin do not appear to be improved compared to other chemotherapeutic regimens tested by SWOG in this patient population.

Original languageEnglish (US)
Pages (from-to)75-78
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume41
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Oncology
Carboplatin
Non-Small Cell Lung Carcinoma
Cells
Cryotherapy
Ice
Mucositis
Toxicity
Appointments and Schedules
Sepsis
edatrexate
Fluids
Survival
Pleural Effusion
Neutropenia
Multicenter Studies
Therapeutics

Keywords

  • Carboplatin
  • Edatrexate
  • Non-small-cell lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Phase II trial of edatrexate plus carboplatin in metastatic non-small- cell lung cancer : A Southwest Oncology Group study. / Gandara, D. R.; Edelman, Martin J.; Crowley, John J.; Lau, Derick H M; Livingston, Robert B.

In: Cancer Chemotherapy and Pharmacology, Vol. 41, No. 1, 1997, p. 75-78.

Research output: Contribution to journalArticle

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abstract = "Background: Edatrexate and carboplatin are each active single agents in the treatment of non-small-cell lung cancer (NSCLC). Preclinical studies in NSCLC lines have demonstrated schedule-dependent synergy of edatrexate followed by carboplatin. In a phase I trial, we demonstrated the tolerability of this combination, the ability of ice-chip cryotherapy to ameliorate dose- limiting mucositis, and promising activity in NSCLC. This phase II trial (SWOG 9207) was undertaken to investigate the efficacy of this regimen in stage IV NSCLC. Methods: A total of 24 patients with stage IV disease were accrued to this Southwest Oncology Group (SWOG) multicenter study. Treatment consisted of edatrexate 80 mg/m2 (50{\%} dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m2 every 28 days. Results: Of the 24 patients, 23 were assessable for toxicity and response; one was ineligible for study entry. Myelosuppression was the most significant toxicity; grade 3-4 neutropenia was seen in 8/23 patients. Two patients died of neutropenic sepsis during the first cycle of therapy, in both instances associated with the presence of pleural effusions. Although mild mucositis was common, it was dose-limiting (grade 3) in only three patients. Objective response was observed in 3/23 patients (13{\%}). The median survival time was 7 months, and 30{\%} of patients remained alive at one year. Conclusions: This study suggests that ice-chip cryotherapy is effective in reducing the severity of mucositis typically associated with this edatrexate schedule of administration. However, unexpectedly severe myelosuppression resulted in death from neutropenic sepsis in two patients with third space fluid collections, leading to a protocol amendment to exclude such patients from study entry. Furthermore, response and median survival with this dose schedule of edatrexate and carboplatin do not appear to be improved compared to other chemotherapeutic regimens tested by SWOG in this patient population.",
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