allopurinol and Neoplasm-Metastasis

We determined the toxicity and preliminary response rate of escalating doses of 5-fluorouracil (670 to 1,500 mg./m.2 per day) combined with a fixed dose of interferon-alpha 2b (5 million units) and allopurinol (300 mg. every 8 hours) in cohorts of patients with metastatic prostate cancer.. The trial included 11 men with metastatic prostate cancer. Cohorts of patients received a 5-day constant infusion of 5-fluorouracil combined with subcutaneous interferon-alpha 2b 3 times weekly and allopurinol for 1 week during 5-fluorouracil infusion. Treatment was repeat every 3 weeks.. Of 10 patients evaluable for treatment response and toxicity 3 had a partial response as judged by significant decreases in prostate specific antigen measurements (mean followup 13.5 months). Significant dose limiting toxicities encountered included mucositis, diarrhea and leukoneutropenia.. Further evaluation of this treatment to determine overall response rates and benefit should take into consideration the significant toxicity experienced.

Topics: Aged; Allopurinol; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms; Recombinant Proteins

5-Fluorouracil (5-FU) remains the most effective chemotherapeutic agent in the management of patients with metastatic colorectal cancer. Leucovorin enhances its efficacy, but also its toxicity. Cited data suggest modulation of 5-FU toxicity by high dose allopurinol. In a prospective randomized trial we assessed the ability of allopurinol in a conventional dose to modulate the toxicity of 5-FU-leucovorin combination without compromising its efficacy in 50 patients with advanced colorectal cancer. Twenty-seven patients were randomized for allopurinol but had no benefit in terms of response or reduced toxicity over the other 23. Survival of responders with colon cancer was longer than that of non-responders (p = 0.013). Although allopurinol failed to reduce 5-FU-leucovorin toxicity, it did not lower its expected efficacy.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Prospective Studies

The oxygenation, the growth rate and the metastatic potential of a solid tumor depend on its vascularization and, in particular, on angiogenesis; a therapeutic approach affecting angiogenesis has been suggested as an alternative to conventional ones. Especially the study of the metabolism in the cells of the vessel wall should be a useful prerequisite for this approach. In this connection, an enzyme histochemical study was performed to characterize the blood vessels in a solid tumor (Ehrlich carcinoma). The following enzymes were considered: (a) alkaline phosphatase, involved in the transcellular phosphate transport and in the response to inflammatory and growth promoting factors; (b) dihydrofolate reductase, involved in the metabolism of tetrahydrofolate (for the synthesis of nucleic acids and the metabolism of serine and glycine); (c) purine nucleoside phosphorylase, involved in the degradation of purines and, in particular, of extracellular ATP and ADP; (d) xanthine oxidoreductase, engaged in the same degradation path and leading to the formation of urate, a strong antioxidant. Various patterns of enzyme activities were observed in the vessel wall. In particular, thin linear capillaries (presumed to be host capillaries penetrating the tumor) were identified for the intense positivity of alkaline phosphatase, dihydrofolate reductase and purine nucleoside phosphorilase; tortuous capillaries with variable diameters (presumed to be induced by angiogenesis from the host vessels) were negative for the alkaline phosphatase and expressed an heterogeneous pattern for the dihydrofolate reductase. All the data suggest a different vessel behaviour concerning the response to cytokines and to inflammatory stimuli.

Topics: Alkaline Phosphatase; Animals; Biomarkers, Tumor; Blood Vessels; Disease Models, Animal; Female; Mice; Neoplasm Metastasis; Neoplasms; Purine-Nucleoside Phosphorylase; Tetrahydrofolate Dehydrogenase; Xanthine Oxidase

The Eastern Cooperative Oncology Group (ECOG) studied 29 patients with advanced measurable colon cancer who were treated with Aminothiadiazole (NSC #4728) 125 mg/m2 intravenously. Allopurinol 300 mg daily was taken by all patients during treatment. Three patients (12%) demonstrated partial responses on this regimen. Hematologic toxicity did not occur. Gastrointestinal toxicity was severe in 16% of patients and consisted primarily of vomiting and diarrhea. No life-threatening toxicity was encountered. A lack of appreciable toxicity together with the few responses seen suggest that further studies at higher dose may be indicated.

Topics: Allopurinol; Antineoplastic Agents; Colonic Neoplasms; Drug Evaluation; Humans; Neoplasm Metastasis; Thiadiazoles

Allopurinol has been shown to ameliorate the myelotoxicity of 5-fluorouracil (5-FU) given as an infusion. To study the potential effectiveness of allopurinol in modifying the toxicity of 5-FU given as a bolus, 8 adult patients with metastatic malignancies were given 11 courses of bolus 5-FU with allopurinol. Allopurinol was administered at a dose of 900 mg/day orally beginning a week prior to the 5-FU therapy and continued a week after the last dose of 5-FU was administered. Three patients received a total of 5 courses of 600 mg/m2 of 5-FU via bolus injection for 4 consecutive days every 28 days. Six patients were given 6 courses of 800 mg/m2 of 5-FU via bolus injection in the same schedule. Gastrointestinal toxicity was mild and no significant neurotoxicity was documented. However, severe myelosuppression occurred at the 800 mg/m2 dosage which led to marked leukopenia in 5 of the 6 patient courses and thrombocytopenia in 1. Gram-negative sepsis developed in 3 of the leukopenic patients with 2 resultant deaths. Allopurinol does not appear to allow clinically significant dose escalation of bolus 5-FU given on this schedule.

Topics: Adenocarcinoma; Adult; Allopurinol; Carcinoma, Squamous Cell; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Gallbladder Neoplasms; Gastrointestinal Diseases; Hematologic Diseases; Humans; Lung Neoplasms; Neoplasm Metastasis; Rectal Neoplasms

Twenty patients with metastatic colon cancer without prior chemotherapy received 2 g/m2 of 5-fluorouracil (5-FU) infused over 24 h for 5 days preceded by allopurinol 900 mg orally for 1 week and then continued during, and for 1 week after the infusion was completed. Fourteen patients were evaluable for both response and toxicity. One patient (14%) achieved a partial response lasting 2 months. No significant hematologic toxicity was seen but 18 of 19 patients evaluable for toxicity developed mucositis resulting in dose reductions in 3 patients and refusal of a second course by 2 additional patients. 5-FU infusions with allopurinol as used in this regimen appear to offer no therapeutic advantage over a conventional dosing schedule.

Topics: Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Evaluation; Fluorouracil; Gastric Mucosa; Humans; Inflammation; Infusions, Parenteral; Male; Middle Aged; Neoplasm Metastasis

Serum xanthine oxidase activity was measured by a radiochemical method in 137 consecutive patients with jaundice of varying etiology and in 40 non-jaundiced patients with liver or other disease. Serum xanthine oxidase was markedly increased, up to 50 times the upper normal limit (mean + 2 S.D.), in 32 out of 34 patients with infectious hepatitis. A slight elevation of serum xanthine oxidase, up to twice the upper normal limit, was found in 2 out of 49 patients with extrahepatic obstructive jaundice and in 4 out of 20 patients with chronic renal failure. In comparison to serum glutamic-oxaloacetic transaminase and lactate dehydrogenase serum xanthine oxidase appeared to be the more sensitive and specific indicator of acute hepatocellular damage.

Topics: Aspartate Aminotransferases; Chronic Disease; Hepatitis A; Humans; Jaundice; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Myocardial Infarction; Neoplasm Metastasis; Xanthine Oxidase

Topics: Adolescent; Allopurinol; Brain Neoplasms; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Female; Humans; Hydroxyurea; Male; Methotrexate; Neoplasm Metastasis; Papilledema; Prednisolone; Vincristine

Topics: Allopurinol; Cyclophosphamide; Humans; Leukemia, Plasma Cell; Male; Middle Aged; Multiple Myeloma; Neoplasm Metastasis; Plasmapheresis; Prednisone; Recurrence; Skin Neoplasms; Testicular Neoplasms; Vincristine

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Breast Neoplasms; Carcinoma; Emergencies; Estradiol; Female; Humans; Hypercalcemia; Male; Neoplasm Metastasis; Neoplasms; Uric Acid

Topics: Allopurinol; Child; Child, Preschool; Dactinomycin; Female; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Nephrectomy; Preoperative Care; Sulfates; Vincristine; Wilms Tumor