A phase II evaluation of pentoxifylline combined with radiation in the treatment of brain metastases.

Pentoxifylline (PTX) has pharmacological properties that suggest potential utility as a radiation sensitizer, and preclinical animal studies have been promising. In a non-randomized phase II trial, we used PTX plus standard-dose external-beam whole-brain radiation treatment (WBRT) in patients with brain metastases. Seventeen patients were entered; 14 received both WBRT and PTX and were considered evaluable. Nine of the 14 completed treatment. Analyzing data on all 14 evaluable patients according to intent to treat, median survival time was 33 days, comparable to published data from historical controls. PTX toxicity was not a common cause of patient dropout, supporting higher PTX doses in future trials.

Effect of chronic oral pentoxifylline administration on murine erythrocyte deformability.

BACKGROUND: Pentoxifylline has been reported to increase radiation sensitivity in vivo. We sought to evaluate whether this effect is mediated by changes in murine erythrocyte flexibility. METHODS: Pentoxifylline was administered via liquid or solid diet to young adult male CF-1 mice for 1-6 weeks. After 1, 3, and 6 weeks of drug administration, plasma levels of pentoxifylline and major derivatives were measured and erythrocyte deformability was assessed by rheoscopy, a technique which permits direct measurement of individual cellular dimensions. RESULTS: Contrary to prior reports, we found no discernible effect of the drug on erythrocyte deformability. CONCLUSIONS: The beneficial effect of pentoxifylline administration on radiation sensitivity in tumor-bearing mice is mediated by other mechanisms.

IR-192, low dose rate endobronchial brachytherapy in the treatment of malignant airway obstruction.

PURPOSE: To assess the value of low-dose-rate endobronchial brachytherapy in the treatment of malignant airway obstruction. METHODS AND MATERIALS: Between September 1986 and April 1989, 39 patients with malignant airway obstruction had 49 catheter placements for an afterloading, low-dose-rate Ir-192 endobronchial brachytherapy. A flexible fiberoptic bronchoscope with fluoroscopic guidance was used for positioning. Thirty-eight of 39 (97%) patients completed the prescribed treatments. Ninety-seven percent had received previous external radiation in doses ranging from 36-60 Gy. One patient had metastatic renal cell carcinoma; the remainder had recurrent lung cancer. Endobronchial laser treatments were given to three patients 2-3 weeks prior to endobronchial brachytherapy. All patients were followed until death. The median dose delivered in 48 of the 49 placements was 20 Gy at 1 cm. RESULTS: Follow-up bronchoscopy was performed in 28 (72%) of 39 patients. Of these, 13 (46%) had a complete response, 12 (43%) had a partial response, and 3 (17%) had a minor response. Dyspnea improved in 30 of 37 patients (82%); hemoptysis in 17 of 19 patients (89%); cough in 31 of 39 patients (79%); and postobstructive pneumonia in 21 of 23 patients (92%). The median survival for the entire group was 5 months (range 1-31 months). CONCLUSION: This technique is simple, well-tolerated and offered significant palliation.

Distribution and metabolism of pentoxifylline in non-tumor-bearing mice.

Pentoxifylline increases tissue oxygen delivery in patients with atherosclerotic arterial disease by several mechanisms, including lowering blood viscosity and increasing erythrocyte flexibility. Since tumor neo-vessels are also abnormal and associated with intra-tumoral hypoxia and, thus, with radiation failure, pentoxifylline might also be useful as a radiation sensitizer. The mouse is frequently used to study such drugs, but the pharmacokinetics of pentoxifylline in the mouse have not been determined. We investigated this in three separate experiments by administering pentoxifylline intraperitoneally, subcutaneously, or orally. Plasma was assayed for the parent drug and its metabolites by capillary gas chromatography. High plasma levels of pentoxifylline and both major derivatives occurred within several minutes after intraperitoneal or subcutaneous injection, but plasma levels were low after oral administration.

Serum levels of pentoxifylline and its metabolites in non-tumor-bearing mice after chronic oral pentoxifylline administration.

Pentoxifylline lowers blood viscosity and increases erythrocyte flexibility in patients with atherosclerosis, thus increasing tissue oxygen delivery. Since tumor neo-vessels are associated with tissue hypoxia, which contributes to failure of radiation therapy, pentoxifylline might also be useful as a radiation sensitizer. Such drugs are often evaluated in the murine model, but serum levels of pentoxifylline and its metabolites have not been determined in the mouse after chronic oral dosing. We investigated this by administering pentoxifylline via liquid diet or solid diet to young adult male CF1 mice for one to six weeks and assaying plasma for the parent drug and its metabolites. At one, three, and six weeks, plasma levels of pentoxifylline and major derivatives were consistently detectable. Mice remained healthy during this period, indicating that ingestion of large amounts of this drug is well tolerated.

Palliative radiation therapy for Kaposi's sarcoma in patients with AIDS.

Kaposi's sarcoma is a common manifestation of AIDS, particularly in young male homosexual patients. Between 1987 and 1988, eight patients with Epidemic Kaposi's sarcoma received palliative radiation therapy. The authors' experience indicates that radiation therapy can provide good to excellent palliation for skin and oropharyngeal lesions.

Treatment of unresectable pancreatic carcinoma using irradiation with concurrent intravenous 5-FU infusion therapy.

Ten patients with unresectable carcinoma of the pancreas who had only bypass surgery to relieve biliary obstruction were treated with radiation therapy to the pancreas and liver with concurrent 5-fluorouracil (5-FU) intravenous infusion therapy. Treatment regimen was three cycles of chemoradiotherapy with a two week rest period between cycles. 5-FU (1,000 mg/m2 per day) was administered by continuous infusion for the first five days of each cycle. In the first cycle radiotherapy was given to the pancreas to 2,000 cGy/10 fractions using 6 to 10 mV x-rays. In the second cycle 2,400 cGy/160 rads/fraction radiation was delivered to the pancreas and whole liver. In the third cycle, 1,600 cGy/160 rads/fraction to a total dose of 6,000 rads, was administered to the pancreatic tumor. All ten patients completed the treatments without interruption. No major side effects were noticed during the course of treatment. Survival ranged from 9 to 16 months and median survival was 11 months. Symptomatic relief was obtained in all 10 patients. One patient who lived for 16 months developed duodenal stenosis and underwent gastrojejunostomy.

Treatment of liver metastases with a combination of chemotherapy and hyperfractionated external radiation therapy.

Twelve patients with liver metastases from colorectal cancer were treated with 5-FUdR hepatic artery, or 5-FU i.v. infusion therapy and hyperfractionated whole liver irradiation (2,100 rad in 14 fractions, two fractions/day over a period of 9 days). All 12 patients tolerated treatments well and no unusual toxicity was noted from this therapy. Response was assessed on completion of treatment and on follow-up examinations by physical examination, repeat liver function tests (LFTS), and CT scans. Symptomatic relief was achieved in all patients. Decreased liver size and improved LFTS were noted in 10/12 (83%) of patients. CT scans showed decrease in size of metastases. Survivals ranged from 16 to 120 weeks. Infusion therapy was given either by implanted infusion pump or continuous i.v. infusion therapy, 5-FUdR 0.3 mg/kg of body weight/day or 5-FU 1,000 mg/m2/day. Hyperfractionated external radiotherapy with concomitant 5-FUdR hepatic artery of 5-FU i.v. infusion therapy for liver metastases was well-tolerated, and both subjective and objective response and quality of survival were noted. Hyperfractionated external beam irradiation with concurrent chemotherapy can be effective in palliating patients with liver metastases.