Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma.
OBJECTIVE
Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer.


METHODS
24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week.


RESULTS
Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6).


CONCLUSIONS



CONCLUSIONS
The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.
Varveris
Haralambos
H
Department of Radiotherapy and Oncology, Medical School of Crete University, Iraclion University Hospital, Greece. varveris@med.uoc.gr
Kachris
Stefanos
S
Mazonakis
Michael
M
Lyraraki
Efrossini
E
Petineli
Effie
E
Varveris
Antonios
A
Fasoulaki
Anastasia
A
Tzedakis
Antonios
A
Kouloulias
Vasilis
V
Zolindaki
Angeliki
A
Vlachaki
Maria
M
D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000627:therapeutic use* / Q000633:toxicity; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*
D004317:Doxorubicin; D002945:Cisplatin