Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas.
BACKGROUND
Previous observations have suggested that leiomyosarcomas, and especially gastrointestinal leiomyosarcomas, may be less responsive to cancer chemotherapy than other histologic types of non-osseous sarcomas; however, this difference has not been characterized well until quite recently, with the recognition of the special identity of gastrointestinal stromal tumors (GIST). Prior to the general acceptance of this new histologic classification, we decided to study patients with gastrointestinal leiomyosarcomas in concert with other leiomyosarcomas for relative responsivity to a combination cytotoxic regimen developed specifically for leiomyosarcomas.


METHODS
Adult patients with advanced leiomyosarcomas received intravenous chemotherapy as outpatients with dacarbazine 750 micrograms/m2, mitomycin 6 mg/m2, doxorubicin 40 mg/m2, and cisplatin 60 mg/m2 on day 0, with granulocyte macrophage colony stimulating factor (GM-CSF, sagramostim) 250 mcg/m2 given s.c. every 12 hr on days -6 to -3 and on days 1-14 of each 4-week treatment cycle. Our original plan to escalate dacarbazine doses to 1000 mg/m2 following cycle one was abandoned after the first six patients because of toxicity.


RESULTS
We studied 21 patients with GIST and 18 patients with other types of leiomyosarcomas, for a total of 131 treatment cycles, with a median of four cycles per patient in each of the two groups of patients. Toxicity was significant, with 33% having grade 3 vomiting at some time during treatment. Grade 3 leukopenia occurred in 42%, and grade 3 thrombocytopenia was observed in 68% of our patients. In one patient, grade 4 pulmonary toxicity developed during the fourth cycle, and this was considered a major factor in her death. Objective tumor regression was observed in one of 21 (1.8%) (95%CI = 0-14.5%) GIST and in 11 of 18 (61%) (95%CI = 38-84%) other leiomyosarcomas, including eight of 10 uterine cases. In five cases, we interrupted chemotherapy to attempt complete surgical excision of residual tumor, and four of the patients were rendered apparently free of disease. Median survivals for the two groups have been similar with 16.7 months (95%CI = 8.8-27.5 months) for the GIST and 17.5 mos (95%CI = 10.9-35.3%) for the other leiomyosarcomas. Three patients with uterine leiomyosarcomas are still alive more than 2 years after completing this chemotherapy and subsequent secondary surgical excision (+/- irradiation) and two of them are free of disease.


CONCLUSIONS
While this regimen is ineffective against GIST, its value against uterine leiomyosarcomas deserves further study in a larger population.
Edmonson
John H
JH
Mayo Clinic, Rochester, MN 55905, USA. edmoj@mayo.edu
Marks
Randolph S
RS
Buckner
Jan C
JC
Mahoney
Michelle R
MR
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
D016685:Mitomycin; D003606:Dacarbazine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor