Continuous intra-arterial cisplatin combined with radiotherapy in locally advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group pilot study

Abstract

The high local failure rate in patients with locally advanced carcinoma of the cervix treated with standard radiation has spurred interest in radiosensitization. Cisplatin is the most active single chemotherapeutic agent in squamous carcinoma of the cervix, and is considered to be a radiosensitizer. Based on a previous single-institution study looking at continuous low-dose intra-arterial cisplatin given throughout planned radiation therapy in patients with advanced carcinoma of the cervix, the Gynecologic Oncology Group initiated a limited access pilot study to assess the feasibility of this treatment method for a group-wide study. Patients with locally advanced squamous carcinoma of the cervix and surgically documented negative periaortic lymph nodes were eligible for the study. During surgical staging, the catheters of a totally implantable pump were placed in the internal iliac arteries. The pump was filled with cisplatin which was delivered at 4.5-6.5 mg day-1 continuously throughout both external radiation and brachytherapy. Drug distribution through the catheters was determined using radiolabelled macro-aggregated albumin particles. Three of nine evaluable patients were free of disease at follow-up. Drug distribution was less than optimal through 4.6% of the pump catheters. Five patients had premature discontinuation of the cisplatin for various reasons. These problems resulted in low accrual and subsequent closure of the study. This treatment method is not feasible for a phase III evaluation on a group-wide basis.

Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

“…It has been doubtful whether appropriate drug distribution is obtained for the tumor. Some investigators have evaluated the blood flow distribution using 99m Tc-MAA from the iliac artery to the pelvis, the tumor, and superior and inferior gluteal parts (20,25,26,38). We used angio-CT to determine whether the tumor was enhanced evenly.…”

“…It is believed that the higher concentration of CDDP perfusing the sacral plexus is the etiologic factor precipitating the neuropathy (18,20). Kavanagh et al (18), LaPolla et al (20), and Roberts et al (26) in a previous study of continuous intra-arterial infusion CDDP with or without the fluorouracil derivative 2-deoxy-5-fluorouridine, noted that 11-37% of patients developed neuropathy of the lower extremity. Because the optimal platinum drug dosage, time interval, and sequence of intra-arterial cisplatin in conjunction with radiation are unknown, neurotoxicity should be carefully documented in the future.…”