Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant interferon alfa (rIFN-alpha) was given to 31 children with acute lymphoblastic leukemia (ALL) in first on-therapy marrow relapse as the sole treatment (30 megaunits/m2/d intravenously x 10 days) before standard four-drug reinduction and during multiagent continuation therapy (30 megaunits/m2 subcutaneously x 3 consecutive days every 3 weeks). After 10 days of rIFN-alpha, there were two partial remissions (PRs); seven additional patients had either greater than or equal to 25% reduction in the percentage of marrow blast cells or hypoplastic marrow. Two patients had progressive disease with an increase in leukocyte counts. All patients experienced influenza-like symptoms, and there were isolated instances of severe abdominal pain and personality change. Dose-limiting toxicity comprised grade III/IV transaminase elevation (two patients) and syncope with personality change (one patient). Twenty-three of 31 children (74%) subsequently achieved marrow remission using standard agents. One patient was taken off study during teniposide (VM-26) and cytarabine (ara-C) consolidation due to toxicity. Continuation therapy including rIFN-alpha pulse was well tolerated in the remaining children; only one patient required rIFN-alpha dosage reduction (for CNS toxicity). rIFN-alpha toxicity did not necessitate reductions in doses of standard chemotherapy agents or significant delays in therapy. Five patients remain in remission at 26+ to 36+ months; 13 patients relapsed in marrow, one in the meninges (7 months), and one in meninges, mediastinum, and lymph nodes (2 months). Two children were removed from study for marrow transplant. In summary, high-dose rIFN-alpha alone had a modest antileukemic effect. In contrast to the clinical experience with combined rIFN-alpha and chemotherapy in adults, rIFN-alpha given in a pulse-like manner throughout continuation therapy did not compromise the intensity of the standard chemotherapy regimen.
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PMID:Recombinant interferon alfa given before and in combination with standard chemotherapy in children with acute lymphoblastic leukemia in first marrow relapse: a Pediatric Oncology Group pilot study. 201 19

A phase I/pharmacokinetic study of the i.p. administration of teniposide (VM 26) was undertaken. Eighteen patients with various malignancies and refractory malignant ascites consented to enter this trial. The dose escalation was made according to the modified Fibonacci scheme. Twenty-four courses were evaluable for toxicity, response and pharmacokinetics. The maximum tolerated dose was reached at 450 mg/m2 and the limiting toxicity was myelosuppression, principally leukopenia. Abdominal pain occurred in one half of the courses but was not limiting. No partial remission, but two 'no change' were achieved for more than 2 months. A reduction or disappearance of ascites was seen in two patients. Pharmacokinetic studies, carried out in all courses, showed that the total exposure for peritoneal cavity averaged 10-fold greater than that of plasma. Based on the outcome of this phase I study, we could recommend phase II studies at a dose of 390 mg/m2 i.p. repeated every 4 weeks with a 4 h dwell-time.
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PMID:Phase I/pharmacokinetic study of intraperitoneal teniposide (VM 26). 273 18

In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combinations of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distention, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.
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PMID:Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia. 391 44

After in vitro tests, a tracer dose of cisplatin was administered to an anuric cancer patient. Plasma total platinum levels were monitored as a function of time, as was filterable platinum elimination by hemofiltration dialysis. Based on the derived pharmacokinetic parameters, the patient was later given 50-mg doses of cisplatin, once as a single agent, then four times in combination with doxorubicin, VM-26, and cyclophosphamide. Plasma levels could be fitted by a sum of three exponentials after the infusion was stopped. The mean corresponding half-lives are 30 minutes, 6 hours, and 5 days. Depending on the rate of infusion, plasma peaks ranged between 1.1 micrograms/ml (5.7 X 10(-6) M) and 2.27 micrograms/ml (1.16 X 10(-5) M). During the hemofiltration process immediately following the infusion, the elimination rate was first-order, with a mean half-life of 60 minutes. The mean amount eliminated during the first hemofiltration session was 8% of the dose, decreasing to about 3% on Days 2 and 3. A partial tumor response was observed after two treatment courses, evidenced by the relief of abdominal pain and bowel obstruction episodes and a 50% decrease in peritoneal metastases.
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PMID:Kinetics of cisplatin in an anuric patient undergoing hemofiltration dialysis. 719 73