Oral metronomic cyclophosphamide in elderly with metastatic melanoma

Borne, E.; Desmedt, E.; Duhamel, Alain; Mirabel, X.; Dziwniel, Véronique; Maire, Cyril; Florin, V.; Martinot, V.; Penel, Nicolas; Vercambre-Darras, S.; Mortier, Laurent

doi:10.1007/s10637-009-9298-5

Cited by 32 publications

(25 citation statements)

References 37 publications

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“…Both the low cost and the oral administration of the drugs are key characteristics of this schedule and may offer important social advantages [4]. Anecdotical case reports [5][6][7] and experiences in small subsets of patients enrolled in retrospective clinical studies [8][9][10] on metastatic cancers have been recently published about the use of metronomic therapy as a first-line treatment. These point out the possible importance of metronomic chemotherapy as an alternative approach to first-line therapy in frail patients requiring palliation or patients refusing the standard chemotherapy for its impact on the quality of life.…”

Section: Introductionmentioning

confidence: 99%

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

et al. 2011

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Metronomic chemotherapy—the low-dose, long term and\ud \ud frequently administered chemotherapy—has revealed in\ud \ud these years an important impact on the stabilization of\ud \ud cancer disease for its known antiangiogenic effects,\ud \ud prolonged clinical benefits and the improved quality of life\ud \ud of several cancer patients, without any high grade toxicity\ud \ud [1–3]. Both the low cost and the oral administration of the\ud \ud drugs are key characteristics of this schedule and may offer\ud \ud important social advantages [4]. Anecdotical case reports\ud \ud [5–7] and experiences in small subsets of patients enrolled\ud \ud in retrospective clinical studies [8–10] on metastatic cancers\ud \ud have been recently published about the use of metronomic\ud \ud therapy as a first-line treatment. These point out the\ud \ud possible importance of metronomic chemotherapy as an\ud \ud alternative approach to first-line therapy in frail patients\ud \ud requiring palliation or patients refusing the standard\ud \ud chemotherapy for its impact on the quality of life. However,\ud \ud no data of prospective clinical trials on first line metronomic\ud \ud chemotherapy are currently available in metastatic\ud \ud cancer human patients.\ud \ud The veterinary medical oncology has advanced dramatically\ud \ud over the past few decades, because of the successful\ud \ud application of a number of conventional chemotherapeutic\ud \ud drugs to the cancer conditions diagnosed in veterinary\ud \ud patients [11]. Veterinary oncology cases often present a\ud \ud unique opportunity to investigate novel drugs and treatment\ud \ud schedules providing many in vivo information to the larger\ud \ud medical community and giving new effective options for\ud \ud dogs themselves [12]. As well recently pointed out by\ud \ud Paoloni and Khanna [13], these studies may also have a\ud \ud great translational relevance, predicting new therapies and\ud \ud related surrogate markers in human beings because pet dogs\ud \ud with cancers might assist the transition between mouse\ud \ud models and human patients. Moreover, in the clinical\ud \ud practice, veterinarians and their clients are generally less\ud \ud willing to accept a high degree of side effects, which most\ud \ud often results in lower drug doses than the ones that are used\ud \ud in human oncology.\ud \ud The aim of the present pilot study was to test a first-line\ud \ud metronomic oral combination of cyclophosphamide (CTX)\ud \ud and celecoxib (CXB) in canine metastatic spontaneous\ud \ud tumours, characterizing possible biomarkers to translate in\ud \ud human clinical research

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Section: Introductionmentioning

confidence: 99%

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

et al. 2011

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“…Interestingly, recent data have suggested that this antiangiogenic effect of metronomic chemotherapy may be also mediated by the induction of the expression of the endogenous inhibitor of angiogenesis thrombospondin (TSP)-1 [18]. The objective of this study was to explore whether metronomic chemotherapy, the activity of which has been already observed in other solid tumor types [19][20][21][22][23][24][25][26][27], warrants further investigation in STS. There is accumulating evidence that antitumor activity of angiogenesis inhibitors is better reflected in terms of parameters of disease stabilization rather than by objective response.…”

Section: Discussionmentioning

confidence: 99%

“Metronomic” chemotherapy in advanced soft tissue sarcomas

Italiano

Toulmonde

Lortal

et al. 2010

Cancer Chemother Pharmacol

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Purpose Angiogenesis plays a crucial role in metastatic progression of soft tissue sarcomas (STS). Endothelial cells are the primary target of metronomic chemotherapy. We report the safety and the efficacy of metronomic chemotherapy in metastatic STS patients. Methods The medical charts of 26 metastatic STS patients treated at Institut Bergonie (Bordeaux, France) with metronomic etoposide (100 mg/day orally for 21 consecutive days, repeated every 4 weeks) were reviewed by two independent investigators. Results Median age was 49. All but three patients received prior treatment with doxorubicin and/or ifosfamide. One patient (4%) had partial response and 11 patients (42%) had stable disease for more than 24 weeks.The 6-month and the 1-year progression-free survival rates were 42% [95% CI: 23; 61] and 23% [95% CI: 7; 39], respectively. The 6-month and the 1-year overall survival rates were 69% [95% CI: 51; 87] and 31% [95% CI: 13; 49], respectively. Two patients experienced grade 4 febrile neutropenia and one of them died of sepsis. Conclusion In this series, metronomic etoposide was associated with significant clinical activity in STS. Further prospective investigations are necessary to identify those patients who are more likely to benefit from this strategy.

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“…The median overall survival for this poor prognosis population was 199 days with cyclophosphamideand144daysformegestrolacetate.Grade3-4 toxicitiesoccurredin4%ofeacharm.Borneetal. [11]treated 13elderlypatients(medianage80years)withmetastaticmelanomawith50-100mgcyclophosphamidedailyduring3of4 weeks. The control rate was 46% with a survival of 4-37 months (median 8 months).…”

Section: Patients With Other Tumorsmentioning

confidence: 99%

Metronomic Oral Cyclophosphamide in Patients with Advanced Solid Tumors

Bojko¹,

Schimmel²,

Bosse³

et al. 2012

Onkologie

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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. Results: All patients had advanced disease with a mean of 2 metastatic sites. Cy was given at a mean dosage of 52 mg daily. Time from diagnosis to start of Cy was 108.6 ± 7.6 months, and from occurrence of metastatic disease to Cy 45.8 ± 45.6 months. Patients had received a mean of 4.2 ± 2.1 prior regimens for metastatic disease. The mean time to treatment failure was 6.4 ± 5.4 months, and mean overall survival was 12.7 ± 7.3 months. Patients received 2.1 ± 1.4 further treatments upon progression. Main toxicities were grade 1 and 2 (n = 25); 3 patients had grade 3 nausea, leucopenia, and elevated gamma glutamyl transferase, respectively. Conclusion: Low-dose oral Cy is a reasonable, generally well tolerated, and inexpensive option for patients with advanced solid tumors.

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Oral metronomic cyclophosphamide in elderly with metastatic melanoma

Cited by 32 publications

References 37 publications

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

“Metronomic” chemotherapy in advanced soft tissue sarcomas

Metronomic Oral Cyclophosphamide in Patients with Advanced Solid Tumors

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