Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven patients with malignant gliomas recurring after surgery and radiation therapy, were treated with high dose BCNU 1 050-1 200 mg/M2 with autologous bone marrow rescue. Four patients also received concomitant 5-fluorouracil 1 000 mg/M2/24 hr daily for three days. Eight of ten evaluable patients demonstrated improvement on CAT scan as well as a decrease in steroid requirement. All patients surviving longer than two weeks after BCNU administration experienced full hematologic recovery. No delayed myelosuppression was seen after a single course of high dose therapy. Two patients died as a result of therapy, one following a second induction of BCNU for a total cumulative BCNU dose of 2 400 mg/M2 and one of infection while cytopenic. Additional toxicity includes one steroid-responsive interstitial pneumonitis, one centrilobular necrosis of the liver which spontaneously resolved and one episode of deep vein thrombosis. With limitation on the maximum BCNU dose and distribution of the total dose over three days, high dose BCNU can be administered with acceptable toxicity. This approach may offer a higher response rate than that expected for standard dose BCNU.
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PMID:High dose BCNU with autologous bone marrow rescue in the treatment of recurrent malignant gliomas. 608 18

Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergistic activity with DNA damaging agents such as cyclophosphamide, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n=12) or relapsed (n=40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n=3, relapsed n=8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (HI; met all criteria for CR except for platelets < 100x10(9)/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%), and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.
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PMID:Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia. 1078 92

CPT-11 is a potent inhibitor of topoisomerase I and has shown antitumor activity in brain xenografts and in clinical trials in recurrent/progressive malignant glioma. VM-26 and VP-16 are topoisomerase II inhibitors and have also shown activity in phase II trials. We performed a phase II trial of intravenous CPT-11 (125 mg/m2) followed 24 h later by VM-26 (125 mg/m2). VP-16 (125 mg/m2) was later substituted for VM-26 due to drug shortage. For patients on anticonvulsants, the starting dose for all drugs was 150 mg/m2. Drugs were given weekly for 3 weeks followed by 1-week rest. Twenty-five patients were entered into the study. Three patients (12%) had improvement in CAT/MRI brain scans (95% confidence interval 3-31%). Fatigue and myelosuppression, mainly leukopenia, were the main toxicities. This combination of the topoisomerase I inhibitor CPT-11 followed by the topoisomerase II inhibitor, VM-26 or VP-16, has shown modest antitumor activity comparable to that reported for each drug singly. Myelosuppression is the main toxicity when topoisomerase I and II inhibitors are combined together.
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PMID:Clinical trial of CPT-11 and VM-26/VP-16 for patients with recurrent malignant brain tumors. 1705 17

Up to now, no consensus has been reached on the standard salvage regimen for patients with refractory or relapsed acute myeloid leukemia (AML). This study was purposed to evaluate the efficacy and safety of combination chemotherapy composing of cyclophosphamide (Cy), cytosine arabinoside (Ara-C) and topotecan (CAT regimen) for 37 refractory or relapsed AML patients. The dosing regimen was as follows: Cy 300 mg/m2 by intravenous infusion, every 12 hours on days 1-3, topotecan 1.25 mg/m2 by intravenous continuous infusion over 6 hours daily on days 2 to 6, Ara-C 500 mg/m2 by intravenous infusion over 2 hours daily for 5 days on days 2-6. The results showed that all patients completed one cycle of chemotherapy. 12 patients (32.4%) achieved complete remission (CR), 2 (5.4%) achieved partial remission (PR), and the 23 remaining patients achieved no remission (NR). The overall response rate (RR) was 37.8%. Among 18 relapsed cases, 6 cases had CR (33.3%), 2 cases achieved PR (11.1%), and 10 cases were with NR (55.6%). Among 19 refractory cases, 6 had CR (31.6%), and 13 (68.4%) were with NR. There was no statistically significant difference in RR between refractory and relapsed groups (31.6% and 44.4%, respectively) (p=0.42). Myelosuppression was universal. Mild non-hematologic toxicities were mainly gastrointestinal, as nausea, vomiting, diarrhea. The incidence of severe (grade III-IV) non-hematologic toxicity, such as oral mucositis and infection was 37.8% and 86.5% respectively. Only one patient died of severe infection during the observation (within 28 days from start of chemotherapy). The time of median follow-up was 4 (0-33) months, the median overall survival (OS) was 4 (1.8-6.2) months. The median OS for responders was longer than that for non-responders (9 vs 2 months respectively, p=0.00). In conclusion, the CAT regimen of lower dose is well tolerated and has certain anti-leukemia effect, and worthy to be further investigated.
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PMID:[Clinical study on regimen cyclophosphamide, Ara-C and topotecan (CAT) in treatment of patients with refractory or relapsed acute myelogenous leukemia]. 1984 Apr 80