Strategies for new drug identification in small cell lung cancer

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Abstract

Small cell lung cancer (SCLC) tends to be highly responsive to initial treatments, but second-line treatments are usually less successful. The response frequency to second-line chemotherapy is considerably lower than that seen with first-line agents. When new agents are evaluated in previously treated patients, response rates have been lower, and it is conceivable that several potentially active agents might have been missed. As a result, the strategy for new drug identification has been questioned, and conflicting approaches to new drug identification have been advocated. These strategies include the use of previously treated patients, incorporation of new agents as part of a combination regimen, use of new agents after a partial response in an attempt to enhance response, and new agents first in previously untreated patients with extensive SCLC. Patients whose disease recurs immediately after treatment rarely respond to subsequent chemotherapy, whereas those who experience a treatment-free period of 3 months or more, may respond to subsequent treatments with reasonable response rates. Use of new agents as part of a combination is inefficient since discerning an effect would require large numbers of randomized patients, and the effect of a new agent could potentially be buried in the combination. Use of new agents after a partial response may produce false negatives because drug resistance may have emerged already. This approach has considerable appeal for identifying biologic agents. Testing new agents in previously untreated patients has the potential of producing higher response rate than would occur in a previously treated group. This approach has been used with considerable success to identify carboplatin, chronic oral etoposide, teniposide, and epirubicin. With careful patient selection and monitoring, a small randomised study comparing a Phase II agent with more conventional combination chemotherapy suggested that initial treatment with an inactive agent did not adversely affect median duration of survival. The disease-related early deaths occurred in the Phase II arm. The approach to new drug development, however, remains an area of uncertainty and controversy. One successful approach has been to offer new agents to those patients who have not received therapy for 3 or more months.

Original languageEnglish (US)
Pages (from-to)S99-S107
JournalLung Cancer
Volume9
Issue numberSUPPL. 1
DOIs
StatePublished - Aug 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Keywords

  • New drugs
  • Small cell lung cancer

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