Phase I/II study of intravenous nedaplatin and intraarterial cisplatin with transcatheter arterial embolization for patients with locally advanced uterine cervical carcinoma.
BACKGROUND
Nedaplatin, a platinum analog with less renal toxicity and similar efficacy for cervical carcinoma, recently has been shown to have a synergistic effect on cervical carcinoma lines in combination with cisplatin. To determine the clinical efficacy of this combination in patients with cervical carcinoma, the authors conducted a Phase I/II study of intravenous nedaplatin and intraarterial cisplatin combined with transcatheter arterial embolization (TAE).


METHODS
Eligibility criteria were as follows: cervical carcinoma (Stages IB2-IV; International Federation of Gynecology and Obstetrics), 16-70 years of age, performance status between 0 and 2, and adequate bone marrow, renal, and hepatic function. Nedaplatin (40-70 mg/m2) was administered intravenously on Day 1 followed by intraarterial administration of cisplatin (70 mg/m2) on Day 3 via both uterine arteries by using the Seldinger method. This then was followed by TAE. This course of treatment was repeated every 3 weeks for 3 cycles.


RESULTS
Patient data were as follows: age 37-68 (median, 55 years) and Stages IB2:4, IIA:3, IIB:2, IIIA:1, IIIB:3, IVA:2 carcinoma. The response to therapy was defined by magnetic resonance imaging as follows: partial response in 60% (9 of 15) of patients, complete response in 40% (6 of 15) of patients, and an overall response rate of 100% (95% confidence interval, 78-100%). Myelosuppression was manageable. Grade 3/4 renal toxicity was observed in 2 patients who received 70 mg/m2 of nedaplatin. Thirteen patients received radical hysterectomy, 1 patient received lymph node sampling, and 11 patients received adjuvant radiotherapy or chemotherapy.


CONCLUSIONS
The maximum tolerable dose was 70 mg/m2 nedaplatin, and the dose-limiting toxicity was renal toxicity. The recommended dose was 60 mg/m2 nedaplatin intravenously followed by 70 mg/m2 cisplatin intraarterially. Intravenous nedaplatin followed by intraarterial cisplatin with TAE appears to be very effective for locally advanced cervical carcinoma.
Adachi
S
S
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya City, Hyogo, Japan. adachi@hyo-med.ac.jp
Ogasawara
T
T
Wakimoto
E
E
Tsuji
Y
Y
Takemura
T
T
Koyama
K
K
Takayasu
Y
Y
Inoue
J
J
Nakao
N
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004621:Embolization, Therapeutic; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000628:therapy
D009944:Organoplatinum Compounds; C053989:nedaplatin; D002945:Cisplatin