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Phase II Trial of Interleukin 2, Interferon α, and 5-Fluorouracil in Metastatic Renal Cell Cancer: A Cytokine Working Group Study
Ist Teil von
Clinical cancer research, 2000-09, Vol.6 (9), p.3442-3450
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2000
Quelle
MEDLINE
Beschreibungen/Notizen
The
purpose of this study was to evaluate the potential efficacy of
alternating two outpatient regimens for the treatment of metastatic
renal cell cancer. These regimens consisted of 4 weeks of
recombinant interleukin 2 (rIL-2) plus IFN-α2B followed
by 4 weeks of 5-fluorouracil plus IFN-α2B. Fifty patients meeting
eligibility criteria of previous Cytokine Working Group studies
were treated on an outpatient basis. Patients received s.c. rIL-2
(Proleukin; Chiron, Emeryville, CA) during weeks 1–4 of the 8-week
regimen. During weeks 1 and 4, the dosage for rIL-2 was 10
MIU/m 2 twice daily on days 3–5, and the dosage for
IFN-α2B (Intron; Schering Plough, Kenilworth, NJ) was 6
MIU/m 2 on day 1. During weeks 2 and 3, the dosage for rIL-2
was 5 MIU/m 2 on days 1, 3, and 5, and the dosage for
IFN-α2B was 6 MIU/m 2 on days 1, 3, 5. During weeks 5–8,
5-fluorouracil (750 mg/m 2 ) was administered once weekly by
i.v. infusion, and IFN-α2B (9 MIU/m 2 ) was administered as
a s.c. injection three times weekly. Throughout the
treatment, an assessment of quality of life was made and a
symptom-distress scale was evaluated.
There were two patients with complete responses (CRs) and seven with
partial responses (PRs) for an objective response rate of 18%
(95% confidence interval, 10–25). The median response duration was 8
months (range, 3–51+ months). The CRs lasted 5 months and 51+ months
and the PRs ranged from 3+ to 18 months. After completing at least one
course of treatment, eight patients (three with PR, one with minor
response, four with stable disease) became CRs after surgery for
remaining metastatic disease. Six remain alive at 43+ to 53+ months,
and 5 remain disease-free since surgery. The median survival of the
study group is 17.5 months, with a maximal follow-up of 53+ months. The
range in survival is 1–53+ months. Toxicity was primarily
constitutional. and treatment modifications were designed to maintain
toxicity at grade 2/3. The most common toxicities during treatment with
IL-2/IFN were fatigue, nausea/vomiting, anorexia, skin reaction,
diarrhea, fever, and liver enzyme elevations. One-third had central
nervous system toxicity (headache, depression, insomnia). During
5FU/IFN treatment, 49 of 50 patients experienced grade 2/3
myelosuppression during course 1. Eight patients experienced grade 4
toxicities. In conclusion, the activity of this alternating regimen is
similar to that of IL-2/IFN alone, given in 4- week cycles. The
addition of 5FU/IFN failed to increase the efficacy and added new
toxicity (myelosuppression). This report does not confirm the results
previously reported for either alternating or simultaneous
administration of these three agents. Because 5FU does not appear to
add to the antitumor activity of IL-2-based therapy for renal cancer,
current efforts are directed toward a Phase III randomized comparison
of high-dose i.v. bolus inpatient IL-2 treatment versus
treatment with outpatient s.c. injection of IL-2 plus IFN.