LOS ANGELES--A modified M.D. Anderson biochemotherapy regimen for
metastatic melanoma that includes interleukin-2 (IL-2) has antitumor
activity and is suitable for testing in a cooperative group setting,
according to analysis of pilot trial data. The pilot study precedes
the larger phase III ECOG/SWOG 3695 intergroup trial that will
compare the regimen to CVD (cisplatin, vinblastine, and dacarbazine).
Speaking at the 34th Annual Meeting of the American Society of
Clinical Oncology and in a subsequent interview, Michael Atkins, MD,
associate professor of medicine, Harvard Medical School, said that
ample data from multiple sites have shown that the combination of
cisplatin-based chemotherapy and IL-2-based immunotherapy can produce
tumor regression in upwards of 50% of patients with metastatic
"At first blush, it is superior to what you see with either
approach given separately," Dr. Atkins said. "The history
of melanoma, however, is replete with promising phase II studies that
turn out to offer no advantage when compared with standard therapy.
So we feel that a phase III trial is called for."
The pilot trial was designed to test the feasibility of using the
inpatient M.D. Anderson biochemotherapy regimen in a cooperative
group-like setting. Investigators modified the regimen, however,
because of concerns about the high incidence of infection in prior
"We added prophylactic antibiotics and removed central lines at
the end of every course of therapy, and used growth factor support to
keep the blood counts up following each treatment," he said.
Antiemetics were also increased, and strict care guidelines were
established for managing nausea, vomiting, hydration status, low
blood counts, low blood pressure, and kidney and electrolyte problems.
Patients received CVD concurrently with IL-2 (9 MIU/m² by
continuous IV infusion on days 1-4) and interferon alfa-2b (Intron A)
(5 MIU/m² on days 1-5, 8, 10, and 12). Routine G-CSF (Neupogen)
and aggressive antiemetics were initiated after patients 7 and 14,
Forty-four patients were enrolled. None had received prior
chemotherapy or IL-2. However, 23 had received prior interferon
(53%), mostly in the adjuvant setting.
Responses were seen in 19 of 42 evaluable patients (45%), with 6
complete responses (14%). Response durations, Dr. Atkins said, ranged
from 1 to more than 14 months, with 7 currently ongoing. Many
responses, however, were of short duration, due largely to a high
incidence of CNS relapse.
Significant toxicities leading to dose modification included
hypotension requiring pressors; grade 3/4 vomiting (12 episodes, but
only 6 episodes in 90 cycles after initiation of the modified
antiemetic regimen); transient renal insufficiency; grade 4
thrombocytopenia (25 episodes, one associated with bleeding);
neu-tropenia with or without fever (14 instances, but only 10 in 121
cycles following routine use of G-CSF); and catheter-related
bacteremia. The most frequent side effects were myelosuppression and nausea/vomiting.
A recent report of the original M.D. Anderson trial of this regimen
without the increased precautions demonstrated much higher toxicity
than that seen in this pilot trial of the modified regimen, Dr.
Atkins commented in an interview.
"We conclude that this modified concurrent biochemotherapy
regimen is active and likely tolerable for use in a cooperative group
setting," he said. Approaches need to be developed for dealing
with CNS relapse, he noted.