Biochemotherapy of advanced metastatic renal-cell carcinoma: results of the combination of interleukin-2, alpha-interferon, 5-fluorouracil, vinblastine, and 13-cis-retinoic acid.
We conducted a phase I/II clinical trial evaluating the sequential outpatient combination of S.C. recombinant human interleukin-2 (rIL-2; given at 10 MIU/m2 b.i.d. on days 3-5 weeks 1 and 4 and at 5 MIU/m2 on days 1, 3, and 5 of weeks 2 and 3), s.c. recombinant human alpha-interferon (rIFN-alpha; given at 6 MIU/m2 on day 1 of weeks 1 and 4 and on days 1, 3, and 5 of weeks 2 and 3 and at 9 MIU/m2 on days 1, 3, and 5 of weeks 5-8), i.v. bolus 5-fluorouracil (5-FU; given at 1,000 mg/m2 once weekly during weeks 5-8), and i.v. bolus vinblastine (given at 6 mg/m2 once weekly during weeks 5 and 8) in conjunction with p.o. 13-cis-retinoic acid (13-C-RA; given at 35 mg/m2 daily during weeks 1-8). Therapy was always given in the outpatient setting. Grade 3 constitutional symptoms (malaise, chills, fevers, anorexia) were observed in 4%-8% of treatment cycles and required a 50% reduction in the doses of rIL-2 and rIFN-alpha. None of the patients experienced major 5-FU-related toxicities such as severe diarrhea and/or stomatitis; up to 20% of patients developed vinblastine-associated peripheral polyneuropathy, which was reversible after the cessation of therapy. 13-cis-Retinoic acid produced no significant side effect; no toxic death occurred. Among 24 patients with progressive metastatic disease, there were 4 complete remissions (lung, lymph nodes) and 6 partial remissions (lung, pleura, liver, lymph nodes, and peritoneal carcinosis), for an overall objective response rate of 42% (95% confidence interval, 22%-63%).(ABSTRACT TRUNCATED AT 250 WORDS)
Atzpodien
J
J
Department of Hematology and Oncology, Medizinische Hochschule Hannover, Germany.
Kirchner
H
H
Duensing
S
S
Lopez Hänninen
E
E
Franzke
A
A
Buer
J
J
Probst
M
M
Anton
P
P
Poliwoda
H
H
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D000276:Adjuvants, Immunologic; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D015474:Isotretinoin; D005472:Fluorouracil