PALM BEACH, Fla. – Isolated chemotherapy made some nonresectable tumors amenable to surgery and relieved pain in those who were not surgical candidates in a series of 75 patients with advanced pelvic carcinomas.
Nearly a third of the patients (22 of 75) responded to the therapy and were able to undergo surgery – adding months to their lives – and those who had the therapy for palliation reported significant pain relief, Dr. Harold Wanebo said at the annual meeting of the Southern Surgical Association.
"Isolated pelvic chemoperfusion (IPP) provides high tissue drug exposure without systemic toxicity, so it gives an excellent opportunity to induce regression of chemoresistant pelvic cancer without severe toxic side effects," he said in an interview.
Dr. Wanebo of the Landmark Medical Center in Woonsocket, R.I., and his colleagues described the results of 134 perfusions performed in 75 patients with advanced pelvic carcinomas. Of those, 59 received the chemoperfusion as neoadjuvant therapy for potentially resectable tumors, and 16 who had nonresectable cancers were given the therapy for palliation of pain.
The therapy is relatively simple, Dr. Wanebo said at the meeting. It starts with an arteriography, during which both balloon-occlusion and infusion catheters are placed into the inferior vena cava through the saphenous femoral vein and into the aorta. Tourniquets around both the upper thighs maintain a high level of chemotherapy agents within the pelvis. Fluoroscopic imaging is used to confirm patency of the catheters, which are then attached to start the infusion.
Patients typically received two treatments, about 30 days apart. Depending on the tumor type, the following agents were administered:
• Paclitaxel 40 mg/m2 plus 5-fluorouracil 1,500-2,000 mg/m2.
• Cisplatin 100 mg/m2 or oxaliplatin 150 mg/m2, with mitomycin (10-20 mg/m2) for epithelial cancers (adenocarcinoma from rectal cancer, squamous cancer of anal canal).
• Paclitaxel (60 mg/m2) and cisplatin (150 mg/m2) for gynecologic cancer (endometrial, ovarian, and bladder cancer).
• Other agents, including doxorubicin, ifosfamide, and phenylalanine mustard (PAM), for melanoma and sarcoma.
Hospital stays ranged from 3 to 4 days. Neutropenia precautions required extended stays (7-12 days).
Advanced rectal cancer was present in 50 patients. Of these, 26 had the procedure as neoadjuvant therapy before a planned pelvic resection; 8 received it for palliation before surgery, and 16 as palliation only after a previous conventional resection. Of the 26 patients, 15 responded with tumors that became locally resectable, and 7 were resected with curative intent. Four required additional surgery to get clear margins. The other 11 patients did not respond to the chemoperfusion therapy; of those, 2 were treated with an implanted infusion device and for 9, the treatment was palliative.
Eight of the 26 patients had an anorectal squamous cell cancer. Of those, five became eligible for surgery and underwent resection, which resulted in a median survival of 15 months and a mean survival of 31 months; one patient was living without disease at 119 months.
Eight of the 26 patients developed resectable tumors but were not resected. Of those, one with sacral invasion had a pathological complete response; the posttreatment biopsy was negative and the planned resection was aborted. Two patients were medically inoperable; three refused the abdominal sacral resection; and two developed pelvic metastases that precluded resection.
Those who had resections survived for a median of 30 months, and those who had treatment for palliation only survived a median of 8 months.
Complications in a small number of patients included a vascular-arterial intraoperative repair, locoregional edema, scrotal edema, ileus with small bowel obstruction, groin hematoma, bladder dysfunction, hematuria, and incontinence. A larger number of patients experienced hematologic problems such as anemia, neutropenia, and thrombocytopenia. Systemic complications included temporary extremity weakness, bronchospasm, and venous thrombosis.
One patient with advanced endometrial cancer died on postprocedure day 7, and two with recurrent rectal cancer died postoperatively on days 8 and 10 after experiencing symptoms such as fever, sepsis, and neutropenia. "This emphasizes need to carefully monitor patients for 9-11 days after IPP to ensure against neutropenia, which can be fatal if not treated properly," Dr. Wanebo said.
Some cancers – such as recurrent rectal cancer, anorectal squamous cell cancers, gynecologic cancers, and melanoma – seemed to respond better to the treatment, Dr. Wanebo said. Patients with sarcoma did not respond as well.
All of the patients who were perfused for palliation experienced significant pain relief lasting for up to 4 months, including 11 of the 14 whose pain had been narcotic resistant. This was probably because the perfusion therapy halted or regressed perineural invasions.
"In these resection specimens, you often see tumor invasion of the nerve roots," Dr. Wanebo said. "It’s really not clear whether the IPP affects this invasion, or somehow disturbs the neural signaling, but the pain relief is significant," he said, adding that the importance of pain relief for patients with advanced cancers can’t be overstated.