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)

Amphotericin B causes suppression of bone marrow (BM) progenitor cells in vitro. Granulocyte colony stimulating factor (G-CSF) enhances the proliferation of myeloid cells. The present study defines the role of G-CSF in preventing amphotericin B-induced myelosuppression. G-CSF increased the proliferative potential of BM and protected against amphotericin B-induced myelosuppression if it was added to the medium during the early phase of exposure of BM to amphotericin B. Monoclonal antibodies to tumour necrosis factor-alpha (TNF) or interferon-gamma (IFN) inhibited the myelosuppression partially; simultaneous presence of both these antibodies completely abrogated this suppression, suggesting that both TNF alpha and IFN gamma were involved in amphotericin-induced myelosuppression. TNF- or IFN-induced suppression of BM was also inhibited by G-CSF. These data suggest that G-CSF prevents the amphotericin B-induced myelosuppression by antagonizing the suppressive effects of TNF and IFN and by enhancing the proliferative activity of BM.
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PMID:Protective effect of granulocyte-colony stimulating factor against amphotericin B-induced myelosuppression in vitro. 752 37

Fifty-five consecutive patients with metastatic breast cancer (MBC) (n = 57) were treated with a combination of levofolinic acid (I-FA) 100 mg/m2 plus 5-fluorouracil (5-FU) 340 mg/m2 i.v. on day 1-3, cyclophosphamide (CTX) 600 mg/m2 i.v. on day 1 and mitoxantrone (DHAD) 12 mg/m2 i.v. on day 1. DHAD dose was progressively escalated by 2 mg/m2/cycle up to 18 mg/m2 in the absence of dose-limiting toxicities. Granulocyte colony stimulating factor (G-CSF) was given s.c. in order to prevent neutropenia. DHAD dosage could be increased to 18 mg/m2 in 66 out of 317 cycles of chemotherapy (21%). In most patients the dose-limiting toxicity was represented by myelosuppression. A statistically significant correlation was found between median white blood cell (WBC) or absolute neutrophil count (ANC) nadir and DHAD dose level. Moreover, a statistically significant correlation was observed between the number of chemotherapeutic cycles, nadir ANC and WBC, and the occurrence of anemia and thrombocytopenia of increasing severity. These data suggest the occurrence of progressive cumulative bone marrow toxicity. Although patients who reached different DHAD levels showed differences in mean dose intensity, such differences were not statistically significant. No correlation was found between the increase in dose intensity and type, rate or duration of objective responses. In patients with metastatic breast cancer the overall response rate was 72% (95% CL 57-84%) with a 18% complete response rate. Median duration of response was 12 and 11 months, respectively, for complete and partial responses. Projected median survival of the whole series of patients with MBC was 18 months. These data demonstrate that the combination of 5-FU with I-FA, CTX and DHAD is very active against MBC. G-CSF use allows the increase DHAD dosage up to 18 mg/m2/cycle, but its use may be linked to the occurrence of sometimes severe cumulative hematological toxicity.
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PMID:Dose intensification of mitoxantrone in combination with levofolinic acid, fluorouracil, cyclophosphamide and granulocyte colony stimulating factor support in advanced untreated breast cancer patients. A multicentric phase II study of the Southern Italy Oncology Group. 909 30

Paclitaxel is an antimicrotubule agent that interferes with cell division. It has demonstrated promising single-agent activity against non-small-cell lung cancer. The purpose of this study was to evaluate the therapeutic effectiveness of paclitaxel in previously untreated patients with extensive stage small-cell lung cancer (SCLC). The study was designed as a two-stage phase II trial. All patients who entered received paclitaxel by intravenous infusion at a dose of 250 mg/m2 during 24 hours. Granulocyte colony stimulating factor was also provided to ameliorate neutropenia. Cycles were repeated at 21-day intervals. Patients who achieved a complete response received a maximum of 10 cycles of treatment, whereas those who achieved a partial response/regression continued treatment until progression or undue toxicity developed. Patients who progressed or maintained stable disease for six cycles were crossed over to cisplatin and etoposide. Forty-three patients entered the study and all were evaluable for analysis. Responses were observed in 23 (53%) of the patients. There was no significant difference in the response rates in patients with measurable or evaluable disease (13/23 versus 10/20, p = 0.76). At the time of analysis, 39 patients had progressed with a median time to progression of 95 days, and 39 patients had died with a median survival of 278 days. The 1-year achieved survival rate was 24%. Significant neutropenia (absolute neutrophil count <1,000/microl) occurred in 24 (56%) of the patients, but only 2 patients experienced severe infection (grade > or = 3), and there were no septic deaths. The results indicate that paclitaxel is active against SCLC. Myelosuppression was the main side effect in this patient population. Response duration was short (median = 3.4 months), which suggests that paclitaxel is not sufficient as a single agent. Further studies of paclitaxel in combination with other agents against SCLC are currently in progress within the North Central Cancer Treatment Group and other cancer treatment groups. Key Words: Paclitaxel-G-CSF-Small-cell lung cancer-North Central Cancer Treatment Group.
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PMID:Paclitaxel and G-CSF in previously untreated patients with extensive stage small-cell lung cancer: a phase II study of the North Central Cancer Treatment Group. 1052 Oct 70