A multicenter trial of interleukin-2 and low-dose cyclophosphamide in highly chemotherapy-resistant malignancies.
The anti-tumor activity of high-dose recombinant interleukin-2 (IL-2) has been demonstrated in several recent preclinical and clinical studies. In an attempt to study possible synergistic effects with low-dose cyclophosphamide (CYC), a phase II clinical trial was initiated in 32 patients, 18 with malignant melanoma (MM) and 14 with renal cell carcinoma (RCC). The recombinant IL-2 (Cetus Corp., Emeryville, Ca, U.S.A.) was given once daily at 3 x 10(6) U/m2, as a 30-min infusion for 14 days in cycle I and for five days twice in cycles II and III, respectively; if tolerated, the dose was escalated to a maximum of 6 x 10(6) U/m2/day; the cycles, separated by 1-week treatment-free intervals, were each preceded by a single i.v. bolus of CYC at 350 mg/m2. The most prominent side-effects encountered in this trial consisted of a capillary leak syndrome, myalgia and fever requiring dose reduction in half of the patients during the first cycle. Given the limit of tolerable toxicities in a standard care unit, the regimen employed achieved minor anti-tumor activity. No objective responses were achieved in patients with RCC and a 15% remission rate (PR + MR) was seen in melanoma patients.
Lindemann
A
A
Department of Hematology, University of Mainz, FRG.
Hoeffken
K
K
Schmidt
R E
RE
Diehl
V
V
Kloke
O
O
Gamm
H
H
Hayungs
J
J
Oster
W
W
Boehm
M
M
Franks
C R
CR
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004804:Eosinophils; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count; D008214:Lymphocytes; D008545:Melanoma / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D008875:Middle Aged; D008991:Monitoring, Physiologic; D015337:Multicenter Studies as Topic; D012074:Remission Induction
D014408:Biomarkers, Tumor; D007376:Interleukin-2; D003520:Cyclophosphamide