BACKGROUND: Despite high initial sensitivity to chemotherapy, TNBC is associated with a poor prognosis, highlighting the need for novel therapeutic strategies. The aim of this multicenter, randomized, open-label phase II trial was to assess the efficacy of ixabepilone as monotherapy, and the combination of ixabepilone with cetuximab, as first-line treatment in patients with triple-negative locally advanced nonresectable and/or metastatic breast cancer. PATIENTS AND METHODS: Women were randomly assigned to receive either ixabepilone (40 mg/m(2)) every 21 days (n = 40), or ixabepilone (40 mg/m(2)) every 21 days with cetuximab (400 mg/m(2) loading dose, followed by 250 mg/m(2)) once weekly (n = 39). The primary end point of the trial was to estimate the response rates of ixabepilone monotherapy and ixabepilone with cetuximab combination therapy. RESULTS: Of 79 randomized patients, 77 were treated. Based on an intent-to-treat analysis, an objective response rate of 30% (95% confidence interval [CI], 16.6-46.5) was observed in the monotherapy arm, and 35.9% (95% CI, 21.2-52.8) in the combination arm. Median progression-free survival was 4.1 months in both treatment groups. Safety findings were consistent with the known individual toxicity profiles of ixabepilone and cetuximab. Skin and subcutaneous tissue disorders were more common with combination therapy, as were discontinuations because of adverse events. CONCLUSION: Ixabepilone monotherapy and the ixabepilone and cetuximab combination demonstrated similar levels of clinical activity in first-line treatment of advanced TNBC, with a predictable safety profile. Further investigation of novel therapies for TNBC is required to improve patient outcomes.

• MeSH
• Adenocarcinoma drug therapy   pathology   MeSH
• Cetuximab MeSH
• Adult MeSH
• Epothilones administration & dosage   adverse effects   MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Neoadjuvant Therapy MeSH
• Disease-Free Survival MeSH
• Disease Progression MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Aged MeSH
• Triple Negative Breast Neoplasms drug therapy   pathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: New agents that are active in patients with metastatic colorectal cancer are needed. Patupilone (EPO906; epothilone B) is a novel microtubule-stabilising agent. METHODS: Patients with advanced colon cancer who progressed after prior treatment regimens received intravenous patupilone (6.5-10.0 mg m(-2)) once every 3 weeks by a 20-min infusion (20MI), 24-h continuous infusion (CI-1D) or 5-day intermittent 16-h infusion (16HI-5D). Adverse events (AEs), dose-limiting toxicities (DLTs), pharmacokinetics and anti-tumour activity were assessed. RESULTS: Sixty patients were enrolled. The maximum tolerated dose (MTD) was not reached in the 20MI arm (n=31), as no DLTs were observed. Three patients in the CI-1D arm (n=26) experienced 1 DLT each at 7.5, 8.0 and 9.0 mg m(-2), but MTD was not reached. However, the prolonged 16HI-5D arm was terminated at 6.5 mg m(-2) after two of the three patients developed a DLT. Diarrhoea was the most common AE and DLT, with increased severity at the higher doses (9.0 and 10.0 mg m(-2)). Grade 3 or 4 diarrhoea was observed in 11 (35%) of the patients in the 20MI arm, 4 (15%) of the patients in the CI-1D arm and 2 (67%) of the patients in the 16HI-5D arm. Patupilone activity was observed in the 20MI arm with a disease control rate of 58%, including four confirmed partial responses. The disease control rate in CI-1D arm was 39%. CONCLUSION: Patupilone given once every 3 weeks as a 20-min infusion had promising anti-tumour activity and manageable safety profile at doses that demonstrated therapeutic efficacy.

• MeSH
• Adult MeSH
• Epothilones administration & dosage   adverse effects   pharmacokinetics   MeSH
• Infusions, Intravenous methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Maximum Tolerated Dose MeSH
• Neoplasm Metastasis MeSH
• Colonic Neoplasms drug therapy   metabolism   pathology   MeSH
• Disease Progression MeSH
• Antineoplastic Agents administration & dosage   adverse effects   pharmacokinetics   MeSH
• Drug Administration Schedule MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase I MeSH
• Research Support, Non-U.S. Gov't MeSH

Chemoterapie je jednou ze základních léčebných metod používaných v léčbě zhoubných nádorových onemocnění. V kombinaci s ostatními léčebnými modalitami dosahuje vynikajících výsledků. Cytostatika se liší různými mechanismy účinku. Jejich neselektivita a toxicita vede ke snaze identifikovat nové molekuly, které by posunuly terapeutické možnosti onkologie. Snahou je vytvořit takové látky, které by využívaly rozdílné pochody mezi zdravými a nádorovými buňkami a snažily se o diferencovanost zásahu. Hormonální terapie je další z onkologických systémových léčebných modalit. Pracuje na principu přítomnosti specifického znaku na nádorové buňce a jeho interakci s hormonálním preparátem. Klinická data prokázala efektivitu hormonální terapie pouze u karcinomu prostaty, karcinomu mléčné žlázy a karcinomu endometria.

Chemotherapy is one of the basic treating modalities applied in the treatment of malignant tumours. It reaches excellent effects in combination with other treating modalities. Cytostatics differ in their mechanisms of effect. Their non-selectivity and toxicity results into effort to identify new molecules that would shift forward therapeutical possibilities of oncology. The effort is to create such substances utilizing different procedures between healthy and oncogenous cells and to try to produce differentiated affect. Hormonal therapy is another oncological system treating modalities. It works on the principle of the presence of a specific feature found on the tumorous cell and its interaction with hormons. Clinical data have proved effectiveness of hormonal therapy only in the prostate cancer, breast cancer and endometrial cancer.

• Keywords
• Ixabepilon, Alimta,
• MeSH
• Diphosphonates pharmacology   MeSH
• Epothilones administration & dosage   therapeutic use   MeSH
• Glutamates therapeutic use   MeSH
• Guanine analogs & derivatives   therapeutic use   MeSH
• Humans MeSH
• Neoplasm Metastasis drug therapy   MeSH
• Tubulin Modulators administration & dosage   therapeutic use   MeSH
• Bone Neoplasms drug therapy   MeSH
• Neoplasms drug therapy   MeSH
• Antimetabolites, Antineoplastic administration & dosage   MeSH
• Antineoplastic Agents administration & dosage   MeSH
• Selective Estrogen Receptor Modulators therapeutic use   MeSH
• Tamoxifen administration & dosage   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Chemotherapy, Adjuvant methods   MeSH
• Folic Acid Antagonists administration & dosage   therapeutic use   MeSH
• Molecular Diagnostic Techniques utilization   MeSH
• Epothilones administration & dosage   therapeutic use   MeSH
• Colorectal Neoplasms drug therapy   MeSH
• Organoplatinum Compounds administration & dosage   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Pyrimidines administration & dosage   therapeutic use   MeSH
• Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors   MeSH
• Thymidylate Synthase administration & dosage   therapeutic use   MeSH
• Publication type
• Collected Work MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• onkologie
• gastroenterologie
• farmakoterapie