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Chemotherapy Plus Irinotecan, Paclitaxel, Carboplatin Shows Activity

Chemotherapy Plus Irinotecan, Paclitaxel, Carboplatin Shows Activity

CHICAGO—Preliminary results of a phase I trial of induction chemotherapy
followed by chemoradiotherapy with irinotecan (Camptosar), paclitaxel (Taxol),
and carboplatin (Paraplatin) showed that this approach is feasible and active
in stage III non-small-cell lung cancer (NSCLC), reported Ann M. Mauer, MD.
The dose-limiting toxicity when combining these three drugs with concurrent
chest radiotherapy was neutropenia, and weekly delivery of the regimen was not
feasible at the originally planned doses. Dr. Mauer is assistant professor of
medicine at the University of Chicago Pritzker School of Medicine in Chicago,

"Both distant and locoregional treatment failures occur and contribute
to mortality in stage III NSCLC. Consequently, combined-modality therapy with
chemotherapy and radiation is now standard care. Newer agents have been
incorporated into both induction chemotherapy and combined chemotherapy and
radiotherapy regimens. The rationale for the combination used in our phase I
trial is that carboplatin, paclitaxel, and irinotecan each demonstrates
significant single-agent antitumor activity in NSCLC, that all three are
radiosensitizers, and that they have non-overlapping toxicities," Dr.
Mauer said.

Doses Had to Be Reduced

Twenty patients with histologically documented stage III NSCLC and no prior
chemotherapy or chest radiotherapy were enrolled. The planned phase I treatment
schema was induction chemotherapy with irinotecan/paclitaxel/carboplatin
(Figure 1) followed by concomitant chemoradiotherapy with
irinotecan/paclitaxel/carboplatin/radiation (Figure 2). "A third step of
surgery, if feasible, was added because some patient became resectable as a
result of chemoradiotherapy," Dr. Mauer said.

"We had planned to dose-escalate irinotecan but had to reduce doses due
to toxicity," Dr. Mauer said.

Concomitant chemoradiotherapy at dose level I (irinotecan 30
mg/m²/wk, carboplatin area under the curve [AUC]
2/wk, paclitaxel 45 mg/m²/wk)produced grade 3 neutropenia in three patients.
Two had treatment delayed because they met the criteria for dose-limiting
toxicity due to failure to achieve white blood cell and neutrophil recovery to
less than or equal to grade 1 toxicity on the day of scheduled chemotherapy.
Treatment at dose level II (irinotecan 30 mg/m²/wk, paclitaxel 45 mg/m²/wk)
produced dose-limiting grade 3 neutropenia in three of six patients treated.
Treatment at dose level III (irinotecan 30 mg/m²/wk, paclitaxel 40 mg/m²/wk)
produced dose-limiting neutropenia in one of six patients treated.

Nonhematologic toxicities during chemoradiotherapy included esophagitis:
grade 3 esophagitis in four of 16 patients, grade 2 in six patients, and grade
1 in six patients. Grade 3 pneumonitis occurred in one patient and grade 2
pneumonitis in one patient, both at dose level II.

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