title: Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma. A multicentre phase II study.
abstract: Twenty-four evaluable patients with metastatic melanoma have been entered in a multicentre Phase II study of two induction cycles of human recombinant interleukin-2 (rIL-2) 18 x 10(6) IU/m2/day continuous i.v. bolus on days 1-5 and days 12-17. Dacarbazine (DTIC) 850 mg/m2 i.v. bolus was given on day 26. The cycle was repeated at five weeks. Maintenance therapy was scheduled three weeks after the completion of the induction treatment, consisting of rIL-2 18 x 10(6) IU/m2/day for five days alternating with DTIC 850 mg/m2 i.v., every three weeks, for a total of 18 weeks. Median age was 44 years (range 23-80), and Karnofsky index was 100 (range 80-100). One patient had received prior chemotherapy with hydroxyurea and one patient had prior radiotherapy. Six patients responded (25%): two had complete responses (CR) and four had partial responses (PR). Stable disease (SD) was seen in five patients. Responses occurred in the following sites: liver 2/9 (22%), lung 3/14 (21%), skin 2/11 (18%), and lymph nodes 3/12 (25%). Duration of CR was 11+ and 13 months. PRs lasted 2, 5, 7, and 11+ months. Of note, time to progression in patients with SD was similar to that of responders: 4, 4, 11+, 11+, and 14+ months. Toxicity included fever, skin rash, fatigue, anorexia, and diarrhoea in most patients. Two patients had a weight gain of more than 10%. Hypotension requiring vasoactive agents or interruption of rIL-2 occurred in four patients, creatinine elevations WHO grade 1-2 in seven patients, and bilirubin elevations WHO grade 1-3 in six patients. One patient developed transient ventricular tachycardia. It appears that rIL-2 and DTIC in this schedule is feasible and effective, but not clearly superior to rIL-2 alone.
authors.affiliation: Rotterdam Cancer Institute, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: E
authors.initials: E
authors.lastname: Shiloni
authors.forename: S
authors.initials: S
authors.lastname: Aamdal
authors.forename: F J
authors.initials: FJ
authors.lastname: Cleton
authors.forename: S
authors.initials: S
authors.lastname: Iacobelli
authors.forename: J T
authors.initials: JT
authors.lastname: Bijman
authors.forename: P
authors.initials: P
authors.lastname: Palmer
authors.forename: C R
authors.initials: CR
authors.lastname: Franks
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D003606:Dacarbazine