Different metronomic treatment schedules

Many different drugs and drug combinations has been used in clinical investigations on "metronomic" chemotherapy. Below, there will be a list of the most used regimens in publicised articles:


1. Cyclophosphamide (the generic name for Sendoxan, Endoxan, Cytoxan, Neosar, Procytox, Revimmune), also known as cytophosphane, is a nitrogen mustard alkylating agent. It is used to treat various types of cancer and some autoimmune disorders. It is a "prodrug"; it is converted in the liver to active forms that have chemotherapeutic activity. It is by far the most used drug for metronomic chemotherapy, and a medline search on "metronomic" and cyclophosphamide gave 97 hits on September 3 2009.  The metronomic dosing is normally 50 or 100 mg/day together with the evening meal. Cyclophosphamide has been used both as single-agent treatment and as a part of a multi-therapy regimen in in vitro, in vivo, and clinical trials.


Clinical trials with single-agent metronomic Cyclophosphamide

Metronomic Cyclophosphamide has been used against

Cyclophosphamide as part of a combination treatment

-Cyclophosphamide with Celecoxib(Celebrex, Celebra) and high dose Dosetaxel(Taxotere)-Prednisone(Prednisolone)

Fontana et al showed in 2009 that Metronomic Cyclophosphamide plus Celecoxib in combination with Dosetaxel and Prednisone is a feasible and tolerable regimen with a very promising preliminary activity on patients with androgen independent Prostate Cancer.


-Cyclophosphamide with intermittent high dose Etoposide

Boszuk et al 42  patients with metastatic breast cancer were treated with metronomic Cyclophosphamide combined with etoposide tablets in standard dose 5 days every third week. The median overall and progression free survival figures were 25 and 10.5 months, respectively. No toxic mortality occurred, and the treatment was well tolerated.

-Cyclophosphamide with Methotrexate and Thalidomide(Neurosedyn)

Colleoni et al showed in 2006 that Metronomic low-dose Cyclophosphamide 50 mg/day together with Methotrexate induced a drop in VEGF (Vascular Endotelial Growth factor), and was effective and minimally toxic. The addition of thalidomide did not improve results but instead increases side effects signifivantly. In a subanalysis of the same study, they also showed that circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy.


-Cyclophosphamide with Thalidomide(Neurosedyn) and Prednisone

Suvannasankha et al gave metronomic Cyclophosphamide with Thalidomide and Prednisone to 35 patients with Multiple Myeloma. 22 patients (62.9%) responded: 7 (20.0%) complete responses, 2 (5.7%) near-complete responses, and 13 (37.1%) partial responses. Eight
patients (22.9%) had stable disease, and three (8.6%) had disease progression. The treatment was well tolerated.


-Metronomic Cyclophosphamide with bolus Cyclophosphamide, Dexamethasone and Celecoxib(Celebrex)

Fontana el al gave twenty-eight patients  with hormone resistant prostate cancer(68% docetaxel-resistant) received 500 mg/m(2) Cyclophosphamide i.v. bolus on day 1 and, from day 2, 50 mg/day Cyclophosphamide p.o. plus 200 mg/twice a day Celcoxib p.o. and 1 mg/day Dexamethasone p.o. until disease progression. A confirmed prostate-specific antigen decrease of >/=50% from baseline was observed in 9 of 28 patients (32%). Median progression-free survival and overall survival were 3 months (95% confidence interval, 2.2-4.2 months) and 21 months (95% confidence interval, 12.4-29.4 months), respectively. Toxicity was mild and no grade 3 to 4 toxicities occurred. 


-The PEP-C regimen

Coleman et al gave 75 oral prednisone 20 mg after breakfast, cyclophosphamide 50 mg after lunch, etoposide 50 mg after dinner, and procarbazine 50 mg at bedtime with an oral antiemetic. Overall, 69% achieved an objective response after PEP-C treatment, with 36% complete responses and 33% partial responses. The regimen was generally well tolerated. 


Preclinical trials showing effect of metronomic Cyclophosphamide


- Cyclophosphamide with Hyperthermia

Borkamo et al have shown that hyperthermia improves the antitumour effect of metronomic cyclophosphamide in a rat transplantable brain tumour.


- Cyclophosphamide with Sunitinib(Sutent) and Lenalidomide(Revlimid)

Blansfeld et al investigated the effect of a combination of metronomic Cyclophosphamide with the anti-angiogenic medicines lenalidomide and sunitinib and was able to halt the progression of tumor growth almost completely in xenograft models of ocular melanoma, colon cancer, pancreatic cancer, and cutaneous melanoma with the three drug combination.


-Cyclophosphamide with Ginseng

Xu et al showed that Ginsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with Cyclophosphamide. Ginsenoside Rg3 and Cyclophoshamide combination reinforced the antitumour effect of each other and improved the living
quality and survival time of mice with ovarian tumours.