Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma: I. Clinical and vascular studies.
A trial of FAA and rIL-2 has been performed both to study the clinical efficacy of this combination and to determine whether they cause haemorrhagic necrosis by acting upon tumour vasculature. FAA and rIL-2 were given to 23 patients with progressing metastatic melanoma. FAA 4.8 gm m-2 was given as a 1 h infusion without urine alkalinisation on days 1, 8 and 15. rIL-2 (6-18 x 10(6) IU/m2/day) was given as a continuous infusion days 8-12 and 15-19 (nine patients) or days 8-12 only (14 patients). Treatment was repeated after 2 weeks unless there was disease progression. Of the 21 assessable patients there have been one complete (skin and liver) and two partial responses (skin and liver, skin and nodes) lasting 20 + 17 + and 15 months, overall response rate 14%. Unexpectedly severe hypotension after the third FAA, when given 2-4 days after RIL-2, was the major toxicity (8/15 grade 3 or 4). No alteration in coagulation parameters were seen during therapy of the first ten patients. No increase in tumour necrosis was seen in any of the 15 biopsies taken from ten patients after therapy. This suggests that FAA does not have similar vascular effects in human as it does in murine tumours.
O'Reilly
S M
SM
Department of Medical Oncology, Charing Cross Hospital London, UK.
Rustin
G J
GJ
Farmer
K
K
Burke
M
M
Hill
S
S
Denekamp
J
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001932:Brain Neoplasms / Q000556:secondary; D004334:Drug Administration Schedule; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D005419:Flavonoids; D007376:Interleukin-2; D011994:Recombinant Proteins; C049328:flavone acetic acid