Intraperitoneal cytosine arabinoside administered in sequence with systemic cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.
After standard management of stage III-IV ovarian cancer patients by surgical reduction of tumor mass and subsequent cisplatin-based combination chemotherapy, eradication of residual intraabdominal disease remains a major clinical problem. In an effort to increase response to therapy without adding marrow toxicity, after laparotomy, 21 stage III-IV ovarian cancer patients were treated with systemic chemotherapy comprising cisplatin, doxorubicin, and cyclophosphamide (PAC) on Day 1 followed by intraperitoneal (ip) cytosine arabinoside (Ara-C) on either Day 8 or 14, every 28 days. Ara-C, an S-phase-specific drug, was administered ip to exploit the pharmacologic advantage of an ip regimen at a time when a possible PAC-induced recruitment of cells into the proliferative pool could further maximize cell kill. Kinetic features of ovarian neoplastic cells recovered from peritoneal washings were monitored during treatment by measurement of the thymidine labeling index (TLI): data from four patients indicate that there is an increase in proliferating cells on Days 8 and 14 after PAC treatment. Toxicity of treatment was acceptable. Although 95% of evaluable patients had more than 2 cm of residual disease, response was observed in 47% of patients. The therapeutic potential of this regimen should be tested in patients with small-volume disease after debulking surgery.
Campora
E
E
Department of Medical Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Bruzzone
M
M
Chiara
S
S
Alama
A
A
Iskra
L
L
Carnino
F
F
Parodi
S
S
Foglia
G
G
Ragni
N
N
Rosso
R
R
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology
D003561:Cytarabine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin