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

Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-FU) given intravenously every day for as long as possible (CF-Mito regimen). After the patient had been discharged from the hospital, the same treatment with CF-Mito was performed except that 180 mg/m2 5-FU was replaced by 400 mg/m2 UFT (a mixture of tegafur and uracil) given orally. A total of 11 patients whose tumor had relapsed during the first-line treatment were given 60 mg/m2 cisplatin, 40 mg/m2 Adriamycin, and 40 mg/m2 methotrexate intravenously every 28 days (PAM regimen). In all, 20 patients received 4-44 (mean, 9.7) courses of CF-Mito over a period of 1.5-24 (mean, 5.3) months. The results obtained in these 20 patients with evaluable lesions included no complete remission (CR), 4 partial remissions (PRs), 9 cases of stable disease (SD), and 7 cases of progressive disease (PD). The PR duration was 1.5-22 (mean, 7.5) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, diarrhea, stomatitis, liver damage, and heart failure. In all, 11 patients received 3-7 (mean, 4.1) courses of PAM over a period of 3-14.5 (mean, 5.2) months. All 11 patients had evaluable lesions, and their responses included no CR, 5 PRs, 3 cases of SD, and 3 cases of PD. The PR duration was 1-3 (mean, 1.6) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, heart failure, and hair loss.
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PMID:Combination chemotherapy for advanced urothelial-tract carcinoma. 139 20

A prospective chemotherapeutic trial using combinations of three drugs consisting of three different protocols was performed in 24 patients with advanced transitional-cell carcinoma of the urothelial tract between April 1981 and August 1986. All patients had histologically proven transitional-cell carcinoma and bidimensionally measurable lesions. The protocol I (PPA) was a 5-day course of treatment with 20 mg/m2 cis-platinum and 5 mg/m2 peplomycin (a derivative of bleomycin) on days 1-5, and 25 mg/m2 adriamycin on day 1. Protocol II (CFMit) was a 10-day course with 3 mg/m2 mitomycin-C and 300 mg/m2 cyclophosphamide on day 1, and 180 mg/m2 5-fluorouracil on days 1-10. Protocol III (PAM) was a 1-day course comprising 60 mg/m2 cis-platinum, 30 mg/m2 adriamycin, and 40 mg/m2 methotrexate. In protocols I and III, the drugs were administered every 4-5 weeks, while in protocol II, the drugs were administered continuously without any interval. Of the 9 patients who received 1 to 5 PPA courses, only 3 patients showed a minor response. In the 10 patients who received 4 to 44 CFMit courses, 3 (33%) achieved partial remission for 1.5-22 months, and 3 had a minor response. Of the 5 patients receiving 3 to 7 PAM courses, 1 patient achieved partial remission for 5 months, and 1 had a minor response. Myelosuppression, nausea, vomiting, and anorexia were frequently observed in each protocol. Loss of hair was often observed in protocols I and III. Stomatitis and diarrhea were observed in protocol II. Three patients in protocol I, 4 patients in protocol II, and 1 patient in protocol III were unable to tolerate more courses of the regimen due to the severe side effects.
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PMID:Three-drug combination chemotherapy for advanced urothelial tract carcinoma. 244 54

In these preliminary experiments, we have found enhanced cell killing by the bifunctional alkylating agent L-phenylalanine mustard (L-PAM) in the presence of inhibitors of poly (ADP-ribose) polymerase (ADPRP) in vitro. In vivo enhancement of the tumoricidal effects of L-PAM was observed with the ADPRP inhibitor nicotinamide (1000 mg/kg), although enhanced myelosuppression was also demonstrated. Nicotinamide also increased the plasma elimination half-life of L-PAM by a factor of at least 2. This alteration of L-PAm pharmacokinetics makes it difficult to assess the role that ADPRP inhibition plays in the enhancement of L-PAM tumor cell killing in vivo.
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PMID:Enhancement of melphalan cytotoxicity in vivo and in vitro by inhibitors of poly (ADP-ribose) polymerase. 609 Mar 66

Peptichemio is a polypeptide complex of L-phenylalanine mustard. Because of structural similarities between melphalan (L-PAM) and Peptichemio a prospective randomized study was done to compare the therapeutic efficacy of these two agents. After failing various combinations of doxorubicin, cyclophosphamide, fluorouracil, methotrexate, and vincristine patients with advanced breast cancer were randomized to receive either Peptichemio or L-PAM. Peptichemio was administered at 75-100 mg/m2 and L-PAM at 30-40 mg/m2 IV q 3-4 week interval. Of 56 evaluable patients, 28 received peptichemio and 28 received L-PAM. There were no objective responses in the L-PAM group, and disease stabilized in four patients (14%). The median duration of stable disease was three months (range, 3-4 months). In the peptichemio group seven patients (25%) achieved a partial remission, one patient (3%) achieved less than partial remission and three patients (11%) had stable disease. The median duration of response was six months (range, 5-7+ months) for responding patients and three months (range, 2-5 months) for stable disease. The major toxicity of both drugs was myelosuppression which was cumulative. In conclusion, peptichemio is an active agent in advanced breast cancer, but L-PAM is ineffective in previously treated patients with metastatic breast cancer.
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PMID:Peptichemio versus melphalan (L-PAM) in advanced breast cancer. 704 74