Current Role of Irinotecan in the Treatment of Non-Small-Cell Lung Cancer

Current Role of Irinotecan in the Treatment of Non-Small-Cell Lung Cancer

Dr. Kelly has provided a complete, well-written review of the current status
and evolving role of irinotecan (CPT-11, Camptosar) as a cytotoxic agent for
patients with non-small-cell lung cancer (NSCLC). Her review clearly
demonstrates the value of irinotecan in this patient population and further
supports the continued development of this agent in concert with other
chemotherapeutic agents, biologically targeted agents, surgery, and/or

Phase III Data Needed

Only a few prospective randomized phase III studies have investigated the
possible advantage of irinotecan over other agents in the treatment of patients
with advanced NSCLC. Certainly, the median survival times reported in individual
studies appear promising, but there are inherent problems in comparing one study
to another, and further confidence in the potential superiority of irinotecan
over several other agents alone or in combination therapy will require
additional phase III trials. Although Dr. Kelly did not specifically mention the
incorporation of irinotecan-based therapy into neoadjuvant or adjuvant studies
in patients with earlier-stage tumors (stages IB, II, resectable IIIA), data
presented in her review suggest that this is also a reasonable approach.

If irinotecan/cisplatin becomes an accepted therapy for patients with
advanced NSCLC or first-line therapy for patients with extensive-stage
small-cell lung cancer (SCLC),[1] it is likely that many oncologists will
substitute carboplatin (Paraplatin) for cisplatin in this regimen. Dr. Kelly
discusses the available data on the combination of irinotecan and carboplatin,
but they are from early studies with small numbers of patients. Further data on
this doublet are clearly needed.

Phase II Doses

Dr. Kelly and associates are conducting a phase I trial of irinotecan and
carboplatin at the University of Colorado. We are completing a
phase I/II trial of the combination at the Sarah Cannon Cancer Center.
Although these data from our study are preliminary, it appears that the
recommended phase II doses will be irinotecan at 60 mg/m2 on days 1, 8, and
15, and carboplatin at an area under the concentration-time curve (AUC) of 4 on
day 1 only, with treatment cycles repeated every 28 days.

Other investigators, as described by Dr. Kelly, have concluded that the
phase II doses are irinotecan at 50 mg/m² on days 1, 8, and 15, and
carboplatin at AUC 5 on day 1, with cycles repeated every 28 days.[2,3] In
addition, Fukuda et al[4] used irinotecan doses of 40 to 60 mg/m² on days 1, 8,
and 15, and carboplatin at AUC 5 on day 1, repeated every 28 days in a
phase I study. It is notable that 11 (85%) of 13 patients with SCLC and 7
(35%) of 20 patients with NSCLC responded in this phase I trial. These
investigators also recommended irinotecan doses of 50 mg/m2 and carboplatin at
AUC 5 for phase II studies.


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