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Efficacy of metronomic chemotherapy with oral cyclophosphamide and methotrexate in patients with non-hodgkin lymphoma: A retrospective analysis at a single institution

Published on Wednesday, 16 September 2026

Abstract

Metronomic chemotherapy is an emerging strategy offering a potentially less toxic yet effective treatment modality.

We evaluated the efficacy and safety of low-dose metronomic (LDM) chemotherapy in relapsed or refractory non-Hodgkin lymphoma (NHL) by retrospectively reviewing the data of 16 NHL patients who were treated with oral cyclophosphamide plus methotrexate (CM) as LDM chemotherapy

The patients received oral cyclophosphamide (50 mg per day) and oral methotrexate (2.5 mg twice weekly) until disease progression or unacceptable toxicity was noted.

Fifteen NHL patients were evaluable in the study. The overall best response rate was 53.3% (2 complete responses and 5 partial responses), with 6.7% of patients achieving stable disease. The median treatment duration was 4.8 months (range, 1.45-25.3 months); the median overall and progression-free survival times were 12.1 and 6.6 months, respectively; and the median response duration was 8.7 months. Only 4 patients were managed with further salvage chemotherapy.

The CM regimen was generally well tolerated, and there was no treatment-related mortality.

We concluded that metronomic therapy with an oral CM regimen administered for continuous, prolonged periods represents a well-tolerated treatment for recurrent NHL, especially in elderly patients.

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About this publication.

The Di Bella's Method: Use of pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea, Melatonin (since 1974), Somatostatin/Octreotide analogues and/or derivatives (since 1977) with prolactin inhibitors Cabergoline and/or Bromocriptine (together with others chemical compounds) in non-Hodgkin Lymphoma (the dosage and administration schedule must be individualised for each patient):

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives since 1977);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

The Di Bella's Method: Use of pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds: the dosage and administration schedule must be individualised for each patient - in several Oncological Pathologies:

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Disease Control after Androgen Deprivation Therapy Combined with Di Bella Multitherapy (Di Bella's Foundation);

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;