Intraarterial cisplatin with intravenous paclitaxel and ifosfamide as an organ-preservation approach in patients with paranasal sinus carcinoma.
BACKGROUND
The objectives of this study were to determine the efficacy, organ-preservation rate, and safety of intraarterial (IA) cisplatin in combination with intravenous paclitaxel and ifosfamide in patients with locally advanced carcinoma of the paranasal sinuses who required orbital exenteration or major craniofacial resection for complete tumor resection.


METHODS
Patients were treated with intravenous paclitaxel (135 mg/m(2)) on Day 1, ifosfamide (1000 mg/m(2)) on Days 1-3, sodium mercaptoethanesulfonate (600 mg/m(2)) on Days 1-3, and IA cisplatin (100 mg/m(2)) on Day 1 every 21 days.


RESULTS
Of 24 study participants, 20 patients received at least 1 course of IA cisplatin, 1 patient had an early death, and 19 patients were evaluable for response. Five of those 19 patients (26%) achieved a complete response (CR), 6 patients (32%) achieved a partial response, and 8 patients (42%) had stable disease or developed progressive disease. Eye-sparing surgery followed by radiotherapy (RT) was feasible in 7 of 24 patients, RT was offered to only 7 patients, whereas 3 patients received chemotherapy and RT, 2 patients refused further therapy, 3 patients underwent craniofacial resection with orbitectomy, and 1 patient was treated systemically for metastatic disease. At the completion of treatment, 14 of 23 patients (61%) with locally advanced disease were disease free, and the orbit was preserved in 21 of 24 patients (88%). The overall survival, progression-free survival, and disease-free survival rates at 2 years were 60%, 50%, and 84%, respectively. Toxicity was substantial, with two patients experiencing cerebrovascular ischemia (one transient and one cerebrovascular accident) and three patients experiencing cranial neuropathy, which was reversible in two patients.


CONCLUSIONS
Despite the encouraging organ-preservation rate, the approach studied resulted in substantial toxicity, and more effective adjunctive therapy is needed. Alternative approaches, including the integration of targeted therapy agents in induction chemotherapy regimens followed by concomitant chemotherapy and RT or eye-sparing surgery, need further exploration.
Papadimitrakopoulou
Vassiliki A
VA
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. vpapadim@mdacc.tmc.edu
Ginsberg
Lawrence E
LE
Garden
Adam S
AS
Kies
Merrill S
MS
Glisson
Bonnie S
BS
Diaz
Eduardo M
EM
Clayman
Gary
G
Morrison
William H
WH
Liu
Diane D
DD
Blumenschein
George
G
Lippman
Scott M
SM
Schommer
Donald
D
Gillenwater
Ann
A
Goepfert
Helmuth
H
Hong
Waun K
WK
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D010255:Paranasal Sinus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide