Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vinorelbine is a semi-synthetic vinca-alkaloid that has been approved in the treatment of advanced breast cancer. Two pharmaceutical forms, intravenous and oral, have been developed and the dose equivalence has been demonstrated to be between 30 mg intravenous and 80 mg oral. Efficacy is similar and tolerability is good in both forms, with more frequent nausea and vomiting with oral vinorelbine. Both induce neutropenia. Vinorelbine can be combined with anthracyclines and taxanes - the main toxicity being neutropenia. It can be used alone or in combination, particularly with capecitabine, in patients previously treated with anthracyclines and taxanes. A synergistic effect has been observed between vinorelbine and trastuzumab in patients with a hyperexpression of HER2 in their tumours.
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PMID:Vinorelbine in breast cancer. 1893 21

Several drugs have been developed and demonstrated similar efficacy in colorectal cancer treatment therefore with choice, time comes for decision. The biologist will have to provide the tools allowing to clarify this choice. Among the tools available, those of pharmacogenetics and pharmacogenomics appear most promising and recent examples allow to illustrate their clinical interest. The pharmacogenetics of anti-cancer agents presents a clinical characteristic, which requires to hold into account the genetic variations not only of host cells but also of those of the tumor cells. Among the most conclusive examples one is that of the prediction of severe neutropenia induced by the irinotecan among patients homozygous for * 28 allele of UGT1A1 enzyme which conjugates SN38 active compound of irinotecan, the other one is the presence of a KRAS mutated allele in tumor cell to predict resistance to anti EGFR antibodies in the treatment of colorectal metastatic cancer.
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PMID:[The biological point of view on pharmacogenetics of anticancer agents in colorectal cancer]. 1900 23

The purpose of this study was to evaluate pathologic complete response (pCR) rates and adverse events with primary systemic therapy (PST) of intermittent weekly paclitaxel and gemcitabine in patients with stage II and III breast cancer. Node-positive patients with stage II and III breast cancer received paclitaxel 80 mg/m(2) followed by gemcitabine 1,200 mg/m(2) on day 1 and day 8, every 3 weeks for four cycles. Postoperatively, four cycles of doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks were given. Of 44 enrolled patients, 73% had stage III breast cancer with 68% hormone-receptor positive and 41% HER2 positive tumors. Eight patients achieved pCR in primary tumors (18%), 11 in axillary nodes (25%), and five in both tumor and axillary nodes (11%). Breast conservation was possible in 28 patients (64%). Grade III/IV toxicities were neutropenia (57%), leukopenia (14%), febrile neutropenia (2%), and headache (2%). In conclusion, PST with intermittent weekly paclitaxel and gemcitabine in patients with stage II/III breast cancer is both well tolerated and effective, showing 18% pCR rate in the breast.
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PMID:Primary systemic therapy with intermittent weekly paclitaxel plus gemcitabine in patients with stage II and III breast cancer: a phase II trial. 1922 76

Among the many chemotherapeutic options for metastatic colorectal cancer, none has shown clear superiority in efficacy. All pharmacologic agents in current use have been associated with adverse events. Frequently reported adverse events associated with the chemotherapeutic agents oxaliplatin, irinotecan, 5-fluorouracil, and capecitabine include acute and chronic neuropathy, hypersensitivity reactions, diarrhea, neutropenia, and hand-foot syndrome. Although biologic agents are seemingly less toxic, toxic effects can also arise with their use; antiangiogenic agents result in hypertension, and EGFR inhibitors can cause severe hypersensitivity, paronychial infections, and more commonly, dermatologic rash. Furthermore, a correlation has been reported for the efficacy of anti-EGFR agents and development of rash. Data indicate that elderly patients with colorectal cancer who have adequate function and performance status, who may previously have been dissuaded from pursuing active therapy solely on the basis of age, should receive the same treatment as younger patients. To enhance the survival of patients with metastatic colorectal cancer, many therapies are administered. Recognition of treatment-emergent toxic effects will, therefore, aid the design and implementation of management strategies that minimize treatment interruption and/or discontinuation, and enhance quality of life for patients.
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PMID:Toxic effects and their management: daily clinical challenges in the treatment of colorectal cancer. 1933 27

Cisplatin and carboplatin have antitumor activity in breast cancer. Satraplatin, an orally bioavailable platinum analog, offers a potential alternative to intravenous chemotherapy. We conducted a multicenter phase II study of this agent as first- or second-line treatment of metastatic breast cancer. Satraplatin 80 mg/m(2) was taken PO Days 1-5 q 21 days in cycles 1 and 2, and if tolerated, increased to 100 mg/m(2) for subsequent cycles. Restaging studies to assess response were performed after every 2 cycles. Between November 2005 and March 2006, 40 patients were enrolled. Baseline characteristics: 48% prior adjuvant chemotherapy, 60% prior chemotherapy for MBC; median age, 62 years (ranges 43-83), 58% ER+/PR+, 23% ER+/PR-, 18% ER-/PR-/HER2-, and 5% HER2+. In 31 patients with measurable disease, there were two partial responses (PR; 6%; 95% CI 0, 15.2); and four patients (13%) had SD > or =6 months for a clinical benefit rate of 19%. Among the subanalysis of seven triple-negative patients with measurable disease, there were 2 SD and 2 PD. Median survival was 15 months and median progression-free survival was 2.7 months. The most common grade 3-4 toxicities were neutropenia (28%) and thrombocytopenia (25%). AEs leading to treatment discontinuation were nausea (n = 3), thrombocytopenia (n = 3), fever (n = 2), and vomiting (n = 2). This phase II study demonstrates oral satraplatin has limited activity as a single agent for MBC. Satraplatin, at a lower dose used in this study, could be combined with other chemotherapy agents in future trials in breast cancer.
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PMID:Results of a phase II open-label, nonrandomized trial of oral satraplatin in patients with metastatic breast cancer. 1945 42

Tyrosine kinase inhibitors (TKI) are effective in the targeted treatment of various malignancies. Imatinib was the first to be introduced into clinical oncology, and it was followed by drugs such as gefitinib, erlotinib, sorafenib, sunitinib, and dasatinib. Although they share the same mechanism of action, namely competitive ATP inhibition at the catalytic binding site of tyrosine kinase, they differ from each other in the spectrum of targeted kinases, their pharmacokinetics as well as substance-specific adverse effects. With variations from drug to drug, tyrosine kinase inhibitors cause skin toxicity, including folliculitis, in more than 50% of patients. Among the tyrosine kinase inhibitors that are commercially available as yet, the agents that target EGFR, erlotinib and gefitinib, display the broadest spectrum of adverse effects on skin and hair, including folliculitis, paronychia, facial hair growth, facial erythema, and varying forms of frontal alopecia. In contrast, folliculitis is not common during administration of sorafenib and sunitinib, which target VEGFR, PDGFR, FLT3, and others, whereas both agents have been associated with subungual splinter hemorrhages. Periorbital edema is a common adverse effect of imatinib. Besides the haematological side effects of most of TKIs like anemia, thrombopenia and neutropenia, the most common extra-heamatologic adverse effects are edema, nausea, hypothyroidism, vomiting and diarrhea. Regarding possible long term effects, recently cardiac toxicity with congestive heart failure is under debate in patients receiving imatinib and sunitinib therapy; however, this observation was probably relate to patients selection, although, TKIs overall appear to be a very well tolerated drug class.
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PMID:Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. 1968 44

Myeloid leukemia in this series corresponds to the myeloid neoplasms of the 4th WHO classification of pathology and genetics of tumor of haematopoietic and lymphoid tissue. The myeloid neoplasms are composed of six categories, which are 1) myeloproliferative neoplasms (MPN), a new category of 2) myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1, 3) myelodysplastic syndrome (MDS)/MPN, 4) MDS, 5) acute myeloid leukemia (AML) and related precursor neoplasms, and 6) acute leukemias of ambiguous lineage. In MPNs without chronic myelogenous leukemia, the genetic marker of JAK2 V617F is added to the diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis. MDS has the new subtype of refractory cytopenia with unilineage dysplasia composed of refractory anemia, refractory neutropenia and refractory thrombocytopenia. AML with t(9; 11) (p22;q23); MLLT3-MLL, AML with t(6;9) (p23; q34); DEK-NUP214, AML with inv(3) (q21q26.2) or t(3; 3) (q21 ; q26.2); RPN1-EVI1 and AML (megakaryoblastic) with t(1; 22) (p13; q13); RBM15-MKL1 are added to the subtype of AML with recurrent genetic abnormalities, and AML with gene mutations of NPM1 and CEBPA are also added as provisional entities of it. The myeloid neoplasms of the 4th WHO classification are comprehensive and seem to be dynamic by incorporating the results of leukemia researches.
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PMID:[Classification of myeloid leukemias]. 1986 Jan 79

The epothilone B analogue, ixabepilone, binds to b-tubulin, is effective for taxane-refractory metastatic breast cancer (MBC), and may be given every 3 weeks or weekly. We evaluated the efficacy of weekly ixabepilone (I) plus trastuzumab (T) and carboplatin (C) as first line therapy in HER2 + MBC. Patients with HER2+ (3+ by IHC or FISH amplified) MBC received I (15 mg/m2 IV) and C (area under the curve, AUC = 2 IV) on days 1, 8, and 15 of a 28-day cycle for a maximum of 6 cycles, plus weekly T (4 mg/kg loading dose then 2 mg/kg IV) during chemotherapy then every 3 weeks (6 mg/kg IV) until disease progression. The primary objective was to determine whether the combination was associated with a response rate (RR) of at least 75%. Fifty-nine patients were treated, and 39 had HER2 overexpression confirmed in a central lab (cHER2+). For all treated patients, objective response occurred in 26 patients (44%; 95% CI 31-58%), median time to progression was 8.2 months (95% CI 6.3-9.9), and median overall survival was 34.7 months (95% CI 25.7 to [not reached]). Results were comparable for cHer2? cancers. Grade 3-4 adverse events included neutropenia (49%), thrombocytopenia (14%), fatigue (12%), nausea (7%), diarrhea (7%), and neuropathy (7%). One patient died from treatment complications during cycle 1. Weekly ixabepilone and carboplatin plus trastuzumab have an acceptable toxicity profile, but are not likely to be associated with an RR of 75% in HER2+ MBC. Efficacy appears comparable to paclitaxel, carboplatin, and trastuzumab.
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PMID:A phase II trial of trastuzumab plus weekly ixabepilone and carboplatin in patients with HER2-positive metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. 2001 54

KIT D816V mutation has been observed in more than 90% of patients with systemic mastocytosis (SM). This mutation constitutively activates the mammalian target of rapamycin (mTOR) signaling pathway. We tested the efficacy of everolimus (RAD001), a novel oral mTOR inhibitor, at a dose of 10 mg daily in an open label, non-comparative Phase II trial for patients with SM. Ten patients were enrolled from April 2007 to October 2008. Median age was 55 years, four were males, seven had indolent and three aggressive SM, and six were previously treated with other agents. Median duration of therapy was 4 months (range 0.2-18). No objective responses were noted. Four patients had a short-lasting subjective improvement in symptoms for a median duration of 3 months (range 3-15). Grade 1-3 diarrhea, mucositis, and neutropenia were the most common adverse effects. No Grade 4 toxicity was noted. In conclusion, everolimus does not result in appreciable clinical activity in patients with SM.
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PMID:Experience with everolimus (RAD001), an oral mammalian target of rapamycin inhibitor, in patients with systemic mastocytosis. 2003 18

Capecitabine (Xeloda, X) and cyclophosphamide (C) can be given orally and they have synergistic effects with nonoverlapping toxicities in preclinical studies. A phase I study of the XC combination therapy was conducted in patients with metastatic breast cancer (MBC) and determined the recommended dose and schedule of 1657 mg/m/day capecitabine and 65 mg/m/day cyclophosphamide given orally for 2 weeks at a 3-week interval. A phase II study of the oral XC regimen was then conducted. This study enrolled patients with HER2-negative MBC who were earlier treated with anthracyclines. XC was given at the recommended doses on a 3-week schedule for at least six courses unless disease progression or unacceptable toxicities occurred. The primary endpoint was the response rate. Progression-free survival, overall survival, and adverse events were investigated as secondary endpoints. Forty-eight patients with the median age of 58 (range 32-72 years) years were registered. Three patients withdrew by choice before starting the treatment. A complete response was obtained in two of the 45 evaluable patients, and partial response in 14, resulting in an overall response rate of 35.6%. The median progression-free survival and overall survival were 199 (115-231) days and 677 (437 approximately ) days, respectively. Grade 3 neutropenia and leukopenia developed in 11%, and that of anemia and thrombocytopenia in 2% patients. Nonhematological toxicities were mild. Hand--foot syndrome was observed in 14 patients but no one had grade 3-4 toxicity. Oral XC combination is effective with acceptable toxicities in patients with MBC.
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PMID:Oral combination chemotherapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: a phase II study. 2007 12


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