Carzelesin phase II study in advanced breast, ovarian, colorectal, gastric, head and neck cancer, non-Hodgkin's lymphoma and malignant melanoma: a study of the EORTC early clinical studies group (ECSG).
OBJECTIVE
In a phase II trial, the activity of carzelesin, a cyclopropylpyrroloindole prodrug analog, was assessed.


METHODS
Carzelesin was used as second- or third-line chemotherapy in patients with breast, ovarian, head and neck cancer and non-Hodgkin's lymphoma, and as first-line chemotherapy in patients with colorectal and gastric cancer and melanoma. The drug was given as a bolus infusion at a 4-weekly dose of 150 microg/m2. A total of 140 patients were entered and a total of 285 courses were administered.


RESULTS
In general, the compound was well tolerated. Myelotoxicity was the most common toxicity. Grade 3 and 4 leukopenia was observed in 18.6% of the courses, neutropenia in 20.3%, thrombocytopenia in 16.2% and anemia in 8.7%. Double nadirs were seen in a total of 41 courses for neutrophils, in 40 for leukocytes and in 3 for platelets. Non-hematological toxicity was very mild. Only one partial response in a patient with melanoma was seen.


CONCLUSIONS
At this dose and schedule carzelesin did not yield activity in the types of tumors studied.
Pavlidis
N
N
Department of Medical Oncology, Medical School, University of Ioannina, Greece. npavlid@cc.uoi.gr
Aamdal
S
S
Awada
A
A
Calvert
H
H
Fumoleau
P
P
Sorio
R
R
Punt
C
C
Verweij
J
J
van Oosterom
A
A
Morant
R
R
Wanders
J
J
Hanauske
A R
AR
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy; D000080890:Duocarmycins; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000009:adverse effects / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D001572:Benzofurans; D000080890:Duocarmycins; D007211:Indoles; D011355:Prodrugs; C076570:carzelesin