Cytotoxic effects of dacarbazine in patients with acute myelogenous leukemia: a pilot study.
METHODS
Preclinical studies performed in our laboratory showed that mouse leukemias become highly immunogenic following in vivo treatment with Decarbazine. This observation led to a successful immunochemotherapy protocol in mice using Dacarbazine plus cytoreductive chemotherapy. Therefore an in vivo and in vitro pilot study was conducted in patients (pts) with resistant or relapsed acute myelogenous leukemia (AML). The DNA-repair enzyme O6-alkylguanine-DNA-alkyl-transferase (OGAT) and the in vitro chemosensitivity to Temozolomide, a Dacarbazine derivative, were evaluated in leukemic blasts.


RESULTS
Nine pts received Dacarbazine (0.4-0.8 g/sqm/day) on days 0, 1 and 2. On day 7, noticeable blast reduction occurred in 4 pts: pt 1 was in partial remission on day 21, pt 6 still showed bone marrow leukemia, pt 8 died of sepsis on day 8, pt 9 is still in aplasia on day 25. Low OGAT levels and consistent sensitivity to Temozolomide in vitro were found in the blasts of pts responsive to Dacarbazine. Subsequently, pts 1-7 underwent Ara-C (1g/sqm/day) plus Mitoxantrone (6mg/sqm/day) treatment for 6 days. Four pts entered complete remission after 27-45 days of aplasia. Failures were due to hypoplastic death, absolute drug resistance, or hypoplasia followed by blast cell regrowth.


CONCLUSIONS
These data point out that Dacarbazine can induce a marked reduction of blast cells as well as severe myelotoxicity in leukemic patients.
Franchi
A
A
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, II Università, Roma, Italy.
Papa
G
G
D'Atri
S
S
Piccioni
D
D
Masi
M
M
Bonmassar
E
E
D000932:Antiemetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy*; D001853:Bone Marrow / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010865:Pilot Projects; D012074:Remission Induction; D000077204:Temozolomide
D000932:Antiemetics; D003606:Dacarbazine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide