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metronomic therapy in carcinoma breast

Yuval Shaked, Elizabeth Pham, Santosh Hariharan, Ksenia Magidey, Ofrat Beyar-Katz, Ping Xu, Shan Man, Florence T H Wu, Valeria Miller, David Andrews, Robert S Kerbel
Conventional chemotherapy drugs administered at a maximum tolerated dose (MTD) remains the backbone for treating most cancers. Low-dose metronomic (LDM) chemotherapy, which utilizes lower, less toxic, doses given on a close regular basis over prolonged periods, is an alternative and better tolerated potential strategy to improve chemotherapy. LDM chemotherapy has been evaluated preclinically and clinically and has shown therapeutic benefit, in both early and advanced stage metastatic disease, especially when used as a maintenance therapy...
October 15, 2016: Cancer Research
Robert S Kerbel
The clinical circumstance of treating spontaneous metastatic disease, after resection of primary tumors, whether advanced/overt or microscopic in nature, is seldom modeled in mice and may be a major factor in explaining the frequent discordance between preclinical and clinical therapeutic outcomes where the trend is "overprediction" of positive results in preclinical mouse model studies. To evaluate this hypothesis, a research program was initiated a decade ago to develop multiple models of metastasis in mice, using variants of human tumor cell lines selected in vivo for enhanced spontaneous metastatic aggressiveness after surgical resection of established orthotopic primary tumors...
July 2015: Cancer Journal
V Petry, D M Gagliato, A I C Leal, R J Arai, E Longo, F Andrade, M D Ricci, J R Piato, R Barroso-Sousa, P M Hoff, M S Mano
Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2- (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m(2) during 8 weeks followed by weekly doxorubicin at 24 mg/m(2) for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose)...
May 2015: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Francesca De Iuliis, Gerardo Salerno, Ludovica Taglieri, Rosina Lanza, Susanna Scarpa
BACKGROUND: Elderly patients with metastatic breast cancer (MBC) have more problems receiving chemotherapy than younger patients, especially with the presence of multiple comorbidities, adverse drug events and functional decline. Low-dose oral administration of cytotoxic agents such as vinorelbine, a semisynthetic vinca alkaloid that interferes with microtubule assembly, leading to arrest of cell division, is usually effective and well tolerated. METHODS: From February 2010 to February 2014, 32 patients with MBC, median age 76 years (range 69-83) were treated with oral vinorelbine 30 mg (total dose), one day on and one day off, until disease progression or unacceptable toxicity levels were reported...
January 2015: Tumori
Gauthier Bouche, Nicolas André, Shripad Banavali, Frank Berthold, Alfredo Berruti, Guido Bocci, Giovanni Brandi, Ugo Cavallaro, Saviero Cinieri, Marco Colleoni, Giuseppe Curigliano, Teresa Di Desidero, Alexandru Eniu, Nicola Fazio, Robert Kerbel, Lisa Hutchinson, Urszula Ledzewicz, Elisabetta Munzone, Eddy Pasquier, O Graciela Scharovsky, Yuval Shaked, Jaroslav Stěrba, Martin Villalba, Francesco Bertolini
The Fourth Metronomic and Anti-angiogenic Therapy Meeting was held in Milan 24-25 June 2014. The meeting was a true translational meeting where researchers and clinicians shared their results, experiences, and insights in order to continue gathering useful evidence on metronomic approaches. Several speakers emphasised that exact mechanisms of action, best timing, and optimal dosage are still not well understood and that the field would learn a lot from ancillary studies performed during the clinical trials of metronomic chemotherapies...
2014: Ecancermedicalscience
Lorenzo Cecconetto, Andrea Casadei Gardini, Elena Tenti, Roberta Maltoni, Sara Bravaccini, Devil Oboldi, Wainer Zoli, Patrizia Serra, Caterina Donati, Samanta Sarti, Dino Amadori, Andrea Rocca
BACKGROUND: Preclinical studies have shown that several chemotherapeutic agents at low doses may affect the vascular system. Here we report the case of a patient with long-term cancer control by metronomic chemotherapy. CASE PRESENTATION: A 62-year-old woman with breast cancer underwent a left mastectomy in July 2007. For a liver metastasis she was given first-line chemotherapy with doxorubicin plus paclitaxel every 21 days. A CT scan after the sixth cycle showed a partial response...
May 2014: Tumori
Evangelos Briasoulis, Gerasimos Aravantinos, George Kouvatseas, Periklis Pappas, Eirini Biziota, Ioannis Sainis, Thomas Makatsoris, Ioannis Varthalitis, Ioannis Xanthakis, Antonios Vassias, George Klouvas, Ioannis Boukovinas, George Fountzilas, Kostantinos N Syrigos, Haralambos Kalofonos, Epaminontas Samantas
BACKGROUND: Metronomic chemotherapy is considered an anti-angiogenic therapy that involves chronic administration of low-dose chemotherapy at regular short intervals. We investigated the optimal metronomic dose of oral vinorelbine when given as monotherapy in patients with metastatic cancer. METHODS: Patients with recurrent metastatic breast (BC), prostate (PC) or non-small cell lung cancer (NSCLC) and adequate organ functions were randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three times a week...
2013: BMC Cancer
Lobna R Ezz El-Arab, Menha Swellam, Manal M El Mahdy
BACKGROUND: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents; including cyclophosphamide (CTX) and capecitabine (Cap) when given at lower doses for prolonged period (metronomic chemotherapy) postulating an antiangiogenic activity as well. AIM OF WORK: To evaluate the action and tolerability of metronomic chemotherapy (MC) and its impact on serum vascular endothelial growth factor (VEGF) levels in metastatic breast cancer (MBC) patients...
March 2012: Journal of the Egyptian National Cancer Institute
Peter Bojko, Gudrun Schimmel, Daniel Bosse, Wolfgang Abenhardt
BACKGROUND: Cure is rarely achieved in patients with advanced metastatic solid tumors, and quality of life including times without burdening therapies is an important endpoint. Metronomic oral cyclophosphamide (Cy) has been studied before and is a reasonable option. PATIENTS AND METHODS: 24 patients with a mean age of 64.4 years (range 36-82 years) were studied. 18 patients had breast cancer, 4 prostate cancer, 1 uterine carcinoma, and 1 carcinoma of unknown primary...
2012: Onkologie
Vittorio Gebbia, Hamouda Boussen, Maria Rosaria Valerio
BACKGROUND: Oral metronomic chemotherapy is a therapeutic option which is particularly attractive due to its ease of administration and low toxic burden. Its mechanism of action probably involves antiangiogenetic effect rather than a classical antiproliferative effect like standard maximally tolerated dose-based regimens. PATIENTS AND METHODS: A retrospective analysis of 61 patients with advanced breast carcinoma was carried out with the aim of reporting activity in terms of response rate, control of tumor-related symptoms, outcome, and toxicity...
February 2012: Anticancer Research
P Fedele, A Marino, L Orlando, P Schiavone, A Nacci, F Sponziello, P Rizzo, N Calvani, E Mazzoni, M Cinefra, S Cinieri
AIM: Registered dose capecitabine monotherapy is active against metastatic breast cancer (MBC), but retrospective analyses indicate that lower doses may be as effective and better tolerated. This study was conducted to assess the safety and efficacy of metronomic capecitabine in heavily pretreated patients with MBC. PATIENTS AND METHODS: In this phase II study 60 MBC patients received continuous metronomic capecitabine monotherapy (1500 mg once a day). Primary endpoint was clinical benefit rate, secondary end points were clinical benefit rates (CBRs), tumour response rates (RRs), overall survival (OS), time to progression (TTP), duration of response (DOR) and toxicity...
January 2012: European Journal of Cancer
A Licchetta, P Correale, C Migali, C Remondo, E Francini, A Pascucci, A Magliocca, A Guarnieri, V Savelli, A Piccolomini, A F Carli, G Francini
Metronomic chemotherapy is an anticancer strategy which uses conventional cytotoxic drugs administered at very low dose in close intervals. We have designed a phase II trial to investigate the safety and antitumor activity of the newest metronomic chemo-hormonal-therapy with daily cyclophosphamide and twice daily megestrol acetate (mCM regimen) in patients with metastatic pretreated breast cancer.Twenty-nine pretreated post-menopausal patients with multiple metastatic sites were enrolled. four patients had a triple negative status, nineteen a positive hormonal ER and PgR status, and three ERB-B2 over-expression...
June 2010: Journal of Chemotherapy
C Damyanov, M Radoslavova, V Gavrilov, D Stoeva
Toxic effects and chemoresistance are serious problems concerning chemotherapy administration. Until now adequate solutions have not been found. In the past few years, while searching for possibilities to decrease toxicity, chemotherapy given in low, frequent doses - a novel strategy called "metronomic" administration - showed promising results. There is also another method for applying low doses of chemotherapeutics at short intervals, called Insulin Potential Therapy (IPT). It combines standard chemotherapy schemes, using lower doses of anticancer drugs and the hormone insulin which is administered intravenously (i...
October 2009: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
V A Chudenko, V M Moiseenko
Although medication of malignancies made a considerable progress and the rates of apparent response grew markedly, those of survival among patients with disseminated solid tumors increased insignificantly. Metronomic therapy with cytostatics is a new modality of treatment via tumor vessels. Dose-dense regimen uses low dosage administration of drugs at regular short intervals (hours, days, weeks). Cumulative dose may be much lower than that used in standard therapy, thus reducing toxicity as well as amount of therapeutic support...
2009: Voprosy Onkologii
Laura Orlando, Anna Cardillo, Andrea Rocca, Alessandra Balduzzi, Raffaella Ghisini, Giulia Peruzzotti, Aron Goldhirsch, Claudia D'Alessandro, Saverio Cinieri, Lorenzo Preda, Marco Colleoni
The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cyclophosphamide (CTX) and methotrexate (MTX) (CM) have been demonstrated. The authors report results and long-term follow-up for patients with metastatic breast carcinoma who obtained prolonged clinical benefit with CM. Prospectively collected data from two successive clinical trials were evaluated. From July 1997 to October 2003, patients with metastatic breast carcinoma were treated with low-dose oral chemotherapy (MTX 2...
September 2006: Anti-cancer Drugs
Joachim Drevs, Julia Fakler, Silke Eisele, Michael Medinger, Gerlinde Bing, Norbert Esser, Dieter Marmé, Clemens Unger
From previous preclinical findings continuous low dose (metronomic) chemotherapy is thought to inhibit tumor angiogenesis. This suggests that activated endothelial cells may be more sensitive to chemotherapeutic drugs than tumor cells. Therefore, we assessed the IC50 for several relevant chemotherapeutic drugs in different endothelial and tumor cell lines to identify optimal compounds to be used for metronomic therapy in a murine renal cell carcinoma model. Adriamycin, idarubicin, 5-fluorouracil, paclitaxel and etoposide were chosen for our studies because of their oral availability in patients or previous reports on metronomic potential...
May 2004: Anticancer Research
Shan Man, Guido Bocci, Giulio Francia, Shane K Green, Serge Jothy, Douglas Hanahan, Peter Bohlen, Daniel J Hicklin, Gabriele Bergers, Robert S Kerbel
A number of recent preclinical studies have sparked interest in the concept of exploiting conventional chemotherapeutic drugs as antiangiogenics. Such antiangiogenic activity is achieved or optimized by metronomic-dosing protocols in which the drug is given at comparatively low doses using a frequent schedule of administration (e.g., once to three times per week) with no breaks, particularly when combined with an endothelial cell-specific antiangiogenic drug. The use of p.o. chemotherapeutic drugs is particularly suitable for this type of treatment strategy...
May 15, 2002: Cancer Research
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