Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC)

Nicolini, Andrea; Mancini, Pa; Ferrari, Paola; Anselmi, L; Tartarelli, G.; Bonazzi, Vanessa; Carpi, Angelo; Giardino, Roberto

doi:10.1016/j.biopha.2004.08.006

Cited by 67 publications

(45 citation statements)

References 17 publications

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“…CP is one of the most effective chemotherapeutic agents used in the treatment of cancers of breast (Levine et al, 2005;Hirano et al, 2008), lung (Sundstrom et al, 2005;Zhang et al, 2006), prostate (Nicolini et al, 2004), ovary (Donato et al, 2004), leukemia (Rao et al, 2005), lymphomas and non-Hodgkin's lymphoma. Significantly different from the CP-treated group using one-way ANOVA followed by the Tukey-Kramer multiple comparisons test (p50.05).…”

Section: Discussionmentioning

confidence: 99%

Modulation of cyclophosphamide-induced early lung injury by allicin

Ashry

Gameil

Suddеk

2013

Pharmaceutical Biology

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Context: Cyclophosphamide (CP) causes lung injury in rats through its ability to generate free radicals with subsequent epithelial and endothelial cell damage. Objective: This study was conducted to assess whether allicin can ameliorate CP-induced early lung injury in rats. Materials and methods: Male Sprague Dawely rats were divided into four groups. Group I was the control group. Group II received allicin (50 mg/kg/d, p.o.) for 14 consecutive days. Group III was injected once with CP (150 mg/kg, i.p.). Group IV received allicin for seven consecutive days, before and after CP injection (150 mg/kg, i.p.). The parameters of study were serum biomarkers, lung tissue antioxidant profile and histopathological changes in lung tissue. Results: A single intraperitoneal injection of CP markedly altered the levels of several biomarkers in lung homogenates. Significant increases in lung content of lipid hydroperoxides were seen that paralleled the decreased levels of total reduced glutathione. Superoxide dismutase activity (SOD) was significantly increased. CP increased the level of serum biomarkers; total protein, lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-a). Pretreatment of rats daily with oral allicin seven days prior to and seven days after CP inject significantly inhibited the development of lung injury, prevented the alterations in lung and serum biomarkers associated with inflammatory reactions, with less lipid peroxidation (LP) and restoration of antioxidants. Moreover, allicin attenuated the secretion of proinflammatory cytokine, TNF-a expression in rat serum. In addition, allicin effectively blunted CP-induced histopathological changes in lung tissue. Discussion and conclusion: Our results suggest that allicin is efficient in blunting CP-induced pulmonary damage.

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Section: Discussionmentioning

confidence: 99%

Modulation of cyclophosphamide-induced early lung injury by allicin

Ashry

Gameil

Suddеk

2013

Pharmaceutical Biology

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“…Previous studies have reported significant stabilising effects of CY but modest if any response to moderate to high doses of bolus CY, although these studies are from the pre-PSA and pre-CT scan era 12 . Metronomic type dosing of CY has been previously reported as a single agent in one 5 patient study 13 but otherwise has been used in combination with potentially immunosuppressive agents such as steroids and conventional doses of cytotoxic agents in prostate and other cancers. We believe that the observed effects of CY were unlikely to be explained 13 purely by the cytotoxic actions of CY at this dose.…”

Section: Discussionmentioning

confidence: 99%

“…Metronomic type dosing of CY has been previously reported as a single agent in one 5 patient study 13 but otherwise has been used in combination with potentially immunosuppressive agents such as steroids and conventional doses of cytotoxic agents in prostate and other cancers. We believe that the observed effects of CY were unlikely to be explained 13 purely by the cytotoxic actions of CY at this dose. Instead, the immunoregulatory and anti-angiogenic effects were probably more likely to explain the data.…”

Section: Discussionmentioning

confidence: 99%

Low Dose Metronomic Oral Cyclophosphamide for Hormone Resistant Prostate Cancer: A Phase II Study

et al. 2007

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Results: Metronomic CY was safe and well tolerated, and although lymphopaenia (up to grade 3) was observed in a third of all patients, there were no clinical complications.The response rate was 34.5% inclusive of objective and PSA (absolute reduction and reduction in PSA velocity). The median duration of response was 7.5 months (range 3-18 months). Conclusions:Oral CY can be used on a metronomic basis safely in men with HRPC.The efficacy, low toxicity, low cost and ease of administration of CY justifies further studies in prostate cancer in combination with other agents.3

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“…In recent years, numerous clinical (44,45) and preclinical studies have been published explaining possible mechanisms of action. For example, low-dose cyclophosphamide may inhibit angiogenesis and hence tumor growth by up-regulating the endogenous inhibitor thrombospondin-1 in tumor, perivascular (11), or tumor-associated stromal cells (46).…”

Section: Discussionmentioning

confidence: 99%

High-Dose Celecoxib and Metronomic “Low-dose” Cyclophosphamide Is an Effective and Safe Therapy in Patients with Relapsed and Refractory Aggressive Histology Non–Hodgkin's Lymphoma

Buckstein

Kerbel

Shaked

et al. 2006

Clinical Cancer Research

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Purpose: Angiogenesis is increased in aggressive histology non^Hodgkin's lymphoma and may be a target with selective cyclooxygenase-2 inhibition and metronomic chemotherapy. Experimental Design: We assessed response, toxicity, and biomarkers of angiogenesis to lowdose cyclophosphamide (50 mg p.o. o.d.) and high-dose celecoxib (400 mg p.o. b.i.d.) in adult patients with relapsed or refractory aggressive non^Hodgkin's lymphoma in a multicenter phase II prospective study. Results: Thirty-two of 35 patients (median age, 62 years) are evaluable for response. Patients had primarily relapsed diffuse large B-cell lymphoma (63%) were heavily pretreated (median of three regimens) and high risk (79% international prognostic index, z2) and 34% were relapsed after autologous stem cell transplant.With a median follow-up of 8.4 months, the overall best response rate is 37% (2 complete clinical response/complete clinical response unconfirmed and 9 partial response), with 22% achieving stable disease. Median overall and progression-free survivals are14.4 and 4.7 months, respectively. The median response duration was 8.2 months.The most common toxicity was skin rash (40%); myelosuppression and gastrointestinal side effects were uncommon. Three patients developed deep vein thromboses and two heavily pretreated patients developed treatment-related acute myelogenous leukemia or myelodysplasia after 3.7 and 12 months of therapy. Circulating endothelial cells and their precursors declined and remained low in responders, whereas plasma vascular endothelial growth factor trended to decline in responding patients but increase in nonresponders.Trough celecoxib levels achieved targeted ''antiangiogenic'' levels. Conclusions: Low-dose cyclophosphamide and high-dose celecoxib is well tolerated and active in pretreated aggressive non^Hodgkin's lymphoma. Close surveillance for arterial and venous thrombotic events is recommended. The decline in circulating endothelial cells and their precursors suggests that this combination may be working by inhibiting angiogenesis but should be validated in a larger patient sample.

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Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC)

Cited by 67 publications

References 17 publications

Modulation of cyclophosphamide-induced early lung injury by allicin

Modulation of cyclophosphamide-induced early lung injury by allicin

Low Dose Metronomic Oral Cyclophosphamide for Hormone Resistant Prostate Cancer: A Phase II Study

High-Dose Celecoxib and Metronomic “Low-dose” Cyclophosphamide Is an Effective and Safe Therapy in Patients with Relapsed and Refractory Aggressive Histology Non–Hodgkin's Lymphoma

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