Tolerability of Metronomic Administration of Lomustine in Dogs with Cancer

10664 Background: The efficacy and the antiangiogenic effect of low dose continous (metronomic) administration of chemotherapy are well known. In thi study we tested the clinical activity of oral Ciclophosphamide (CTX) and Methotrexate (MTX) in advanced breast cancer (ABC). Methods: From november 2004 to september 2005 35 ABC patients were enrolled. Median age 59 (range 36–74), ECOG PS 0–2. All patients received at least two prior chemotherapeutic regimens (range 2–4). Metastatic sites were as follow: liver (16), lung (6), bone (9) and skin (4). patients with CNS involvement were excluded. All patients received CTX at the dose of 50 mg/die and MTX at the dose of 2.5 mg twice daily on days 3 and 4 of each week. After two months of treatment patients were re-evalated for disease response. Results: All patients were evaluable for response. After 2 months of treatment we observed 3 PR (8.5%) and 12 SD (34%), for an overall RR of 42%. 23 patients experienced PD. On the whole treatment was well tolerated, with mild toxicity; no patients discontinued treatment due to toxicity. Grade 2 or 3 neutropenia was observed in 14/35 patients and grade 2 trombocytopenia was observed in 9/35 patients. No grade 4 toxicity was observed. Conclusions: Metronomic administration of chemotherapy is well tolerated even in pretreated patients and shows moderate activity in advanced breast cancer No significant financial relationships to disclose.

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Circulating endothelial cells (CECs), progenitors (CEPs), and circulating tumor cells (CTCs) for prediction of response in patients with advanced breast cancer (ABC) receiving metronomic oral vinorelbine (oV): Preliminary results

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14572 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14572-e14572

Author(s):

F. Nole ◽

E. Munzone ◽

F. Bertolini ◽

M. T. Sandri ◽

G. Petralia ◽

...

Keyword(s):

Endothelial Cells ◽

Ct Perfusion ◽

Response Prediction ◽

Circulating Endothelial Cells ◽

Oral Vinorelbine ◽

Indirect Measure ◽

Angiogenic Therapy ◽

Microtubule Inhibitors ◽

Metronomic Administration ◽

Preclinical And Clinical Studies

e14572 Background: Metronomic administration of chemotherapy given once or more per week with no extended gaps was shown to be effectively anti-angiogenic, causing growth arrest or apoptosis of endothelial cells in tumor neo-vessels. Preclinical and clinical studies indicate that ultra-low concentrations of various microtubule inhibitors inhibit proliferation or migration of endothelial cells. We investigated in a phase II study the activity of metronomic administration of oV in ABC, kinetics and response prediction of CECs, CEPs, CTCs and of other biomarkers of angiogenesis (soluble VEGF, VEGFr2, TSP1, bFGF). CT perfusion scans were also performed. Methods: From February 2008, 47 pts with ABC received oV (50 mg/die TTW). Currently 20 pts are evaluable for both activity and biomarker assessment. Baseline levels of biomarkers of angiogenesis were correlated with clinical response. Results: Shown in Table . Conclusions: We found that the baseline value of apoptotic cells (expressed as % of total cells) was significantly correlated with outcome. The baseline total, viable, and apoptotic CEC count and CTCs might provide an indirect measure for angiogenic turnover and an indicator of better response to anti-angiogenic therapy, supporting the use of metronomic treatments in patients expressing high levels of baseline CECs. Updated results will be presented together with correlation with perfusion CT scan and levels of CTCs. [Table: see text] No significant financial relationships to disclose.

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Oral metronomic administration of cyclophosphamide and vinorelbine in previously treated patients with metastatic breast cancer: Phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.e11017 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. e11017-e11017

Author(s):

M. A. Pluma Jimenez ◽

M. Perez ◽

Y. L. Bautista Aragon ◽

R. Villalobos ◽

S. Rivera ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Metastatic Breast ◽

Previously Treated Patients ◽

Previously Treated ◽

Metronomic Administration

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Temozolomide metronomic schedule with weekly of cisplatin in metastaticsoft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e21519 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e21519-e21519

Author(s):

Tanweer Shahid ◽

Vikash Agarwal ◽

Saumen Basu ◽

Gouri Shankar Bhattacharyya

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Performance Status ◽

Progression Free Survival ◽

Median Number ◽

Oral Route ◽

Prognostic Features ◽

Metastatic Soft Tissue Sarcoma ◽

Grade 3 ◽

Metronomic Administration

e21519 Background: Dacarbazine (DTIC) is the standard treatment for metastatic soft tissue sarcoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine but potential for resistance exist. Metronomic administration of TMZ might be a way to overcome resistance. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Methods: We reviewed data of metastatic soft tissue sarcoma patients treated at our Institutions with cisplatin (25 mg/m2 every 7 days for 3 out of 4 weeks) plus TMZ (50 mg/m2/day from day 2 for 27days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases and grade 2 in 10 cases, respectively. Other toxicities included thrombocytopenia (1 case grade 3 and 2 cases grade 2), anemia (1 grade 3 and 2 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 9 patients had a partial response (27.3%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI: 16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic soft tissue sarcoma are encouraging, in light of the negative prognostic features of treated patients.

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Metronomic Chemotherapy in Triple-Negative Metastatic Breast Cancer: The Future Is Now?

International Journal of Breast Cancer ◽

10.1155/2017/1683060 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

M. E. Cazzaniga ◽

L. Cortesi ◽

A. Ferzi ◽

L. Scaltriti ◽

F. Cicchiello ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Metastatic Breast ◽

Metronomic Chemotherapy ◽

Chemotherapy Agent ◽

New Ideas ◽

Metronomic Administration ◽

Chemotherapy Agents ◽

Drug Free ◽

Reporting Data

Triple-negative breast cancer (TNBC) shows a very bad prognosis, even in early stages of disease. Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. In the present article, we review preclinical and clinical data of metronomic administration of chemotherapy agents with or without biological agents in TNBC cell lines and patients, contextually reporting data from the VICTOR-2 study in the subgroup of patients with TNBC, in order to stimulate new ideas for the design of clinical trials in this subset of patients.

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Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer

Indian Journal of Cancer ◽

10.4103/0019-509x.117032 ◽

2013 ◽

Vol 50 (2) ◽

pp. 122 ◽

Cited By ~ 7

Author(s):

K Prabhash ◽

V Noronha ◽

VM Patil ◽

A Joshi

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung ◽

Metronomic Administration

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Metronomic administration of the drug GMX1777, a cellular NAD synthesis inhibitor, results in neuroblastoma regression and vessel maturation without inducing drug resistance

International Journal of Cancer ◽

10.1002/ijc.25206 ◽

2010 ◽

pp. NA-NA ◽

Cited By ~ 1

Author(s):

Dieter Fuchs ◽

Alejandro Rodriguez ◽

Sara Eriksson ◽

Rolf Christofferson ◽

Christian Sundberg ◽

...

Keyword(s):

Drug Resistance ◽

Synthesis Inhibitor ◽

Nad Synthesis ◽

Vessel Maturation ◽

Metronomic Administration

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Metronomic schedule of temozolomide with conventional dose of cisplatin in metastatic melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e20009 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e20009-e20009

Author(s):

E. Simeone ◽

A. Daponte ◽

G. De Feo ◽

V. Montesarchio ◽

V. Chiarion-Sileni ◽

...

Keyword(s):

Metastatic Melanoma ◽

Performance Status ◽

Primary Melanoma ◽

Progression Free Survival ◽

Median Number ◽

Oral Route ◽

Prognostic Features ◽

Conventional Dose ◽

Grade 3 ◽

Metronomic Administration

e20009 Background: Dacarbazine (DTIC) is the standard treatment for metastatic melanoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Metronomic administration of TMZ might be another way to overcome resistance. Patients and Methods: We reviewed data of metastatic melanoma patients treated at our Institutions with cisplatin (75 mg/m2 every 28 days) plus TMZ (75 mg/m2/die from day 2 for 21 days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); primary melanoma was ulcerated in 19 cases (58%); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases each and grade 2 in 16 and 9 cases, respectively. Other toxicities included thrombocytopenia (2 case grade 3 and 3 cases grade 2), anemia (1 grade 3 and 4 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 6 patients had a partial response (18.2%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI:16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic melanoma are encouraging, in light of the negative prognostic features of treated patients. We are now planning a formal phase II study. [Table: see text]

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