Di Bella Multitherapy

Di Bella Multitherapy

Di Bella Multitherapy

Common Names

  • Di Bella's tetralogy
  • DBM
  • Di Bella regimen

For Patients & Caregivers

Di Bella Multitherapy, based on an unconfirmed theory, has been proven ineffective as a cancer treatment.

The Di Bella Multitherapy was developed by the Italian physician Luigi Di Bella in the 1990s. This treatment was very popular in Italy, despite the fact that clinical trials have not shown that it works. It is based on the unconfirmed theory that cancers, especially lymphomas and leukemias, are stimulated to grow by the hormones prolactin and growth hormone. By giving low-dose chemotherapy along with treatments that would lower prolactin and growth hormone levels, Di Bella reasoned that his therapy could help stimulate the body’s self-healing without the toxicity of conventional chemotherapy. He has not provided sufficient evidence, however, to back up these claims. The Di Bella Multitherapy includes:

  • Somatostatin, an inhibitor of growth hormone
  • Melatonin, a hormone that mediates the sleep-wake cycle and is also an antioxidant. Laboratory and animal studies of melatonin suggest a possible anti-cancer activity, but no studies in humans have shown such an effect. See melatonin monograph for additional information.
  • Bromocriptine, which inhibits the secretion of prolactin from the pituitary gland.
  • A solution of retinoic acid, vitamin A, beta carotene, and vitamin E. These retinoids are antioxidants, and independently have shown benefit in clinical trials of promyelotic leukemia and cutaneous T-cell lymphoma.

Di Bella’s theory about cancer has not been confirmed, and the clinical trials that have been performed with this therapy do not provide any support for it.

  • To treat Alzheimer’s disease
    No scientific evidence supports this use.
  • To treat cancer
    Clinical trials do not support this use.
  • To treat Lou Gehrig’s disease (amyotrophic lateral sclerosis)
    There is no evidence to support this claim.
  • To treat multiple sclerosis
    No scientific evidence supports this use.
  • To treat retinitis pigmentosa
    This use is not backed by research.
  • You are taking opioid mediation (such as percocet, codeine, oxycodone, morphine, or methadone) (Somatostatin can lessen or eliminate their effects).
  • You are taking immunosuppressants (such as cyclosporine or tacrolimus) (Bromocriptine might inhibit the metabolism of these medications in the liver, leading to higher-than-normal blood levels that can cause toxicity).
  • You are taking macrolide antibiotics (These can worsen the side effects of bromocriptine).
  • You are taking efavirenz (This medication can increase the effect of bromocriptine).
  • You are taking protease inhibitors (Bromocriptine can heighten their effect).
  • You are taking anti-hypertension drugs (Bromocriptine can lower blood pressure even further).
  • You are taking nifedipine (Melatonin, when taken at the same time, can cause high blood pressure and increased heart rate).
  • You are taking fluvoxamine (This medication can increase blood levels of melatonin, resulting in sedation).
  • You are taking digoxin (Cyclophosphamide decreases the effects of digoxin).
  • You are taking St. Johns wort (This herb can decrease the effect of cyclophosphamide).
  • Increased pain at tumor site in advanced cancer patients
  • Increased sleepiness
  • Diarrhea
  • Nausea
  • Vomiting
  • Loss of appetite
  • Low blood sugar
  • Edema (swelling) of the ankles and feet
  • Anemia
  • Thrombocytopenia (low platelet count)
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For Healthcare Professionals

Questionable alternative therapy comprised of somatostatin, melatonin, bromocriptine, a solution of retinoids, and low doses of cyclophosphamide or hydroxyurea. Physiologist Luigi Di Bella developed the regimen and promotes it as an effective treatment for cancer, retinitis pigmentosa, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease. Treatment is tailored to the individual patient, and purportedly stimulates the body’s self-healing without the toxicity of conventional chemotherapy.

Di Bella multitherapy (DBM) is based on the theory that growth hormone (GH) and prolactin are involved in neoplastic growth. Somatostatin and its analog octreotide inhibit GH and IGF-1 secretion in humans (1), while bromocriptine is a prolactin inhibitor (6). This treatment was very popular in Italy in the late 1990s as Di Bella claimed he cured thousands on an outpatient basis and physicians in other countries, such as Canada, also prescribed it. DBM was highly publicized and politicized in Italy, raising the issue of “freedom of treatment” for patients who could not afford the expensive regimen. In response, local judges ordered that somatostatin be added to the list of effective reimbursable medications (21)(22), and the Italian National Institute of Health supported 11 separate open-label uncontrolled phase II studies of 8 different cancers, organized by Di Bella and the National Cancer Advisory Committee (20). These trials found no complete responses (23)(24), 0.8% partial response rate, and considerable toxicity (12)(18). However, an uncontrolled study of 20 patients with late stage non-Hodgkin’s lymphoma had a 70% response rate with a similar regimen (6).
Adverse effects include increased pain at tumor site, nausea, vomiting, anorexia, diarrhea, and somnolence (6). Somatostatin may reduce or eliminate the efficacy of painkillers (e.g., methadone, morphine) (11).

  • Alzheimer’s disease
  • Cancer treatment
  • Lou Gehrig’s Disease
  • Multiple sclerosis
  • Retinitis pigmentosa

The Di Bella Multitherapy is based on the theory that growth hormone (GH) and prolactin are involved in neoplastic growth, particularly in lymphomas and leukemias. The following components have been studied, but their combined activities and at the Di Bella doses are unknown.

Somatostatin inhibits growth hormone (GH) secretion. Its synthetic analog, octreotide, shows antineoplastic activity in vitro and in vivo, and is used clinically for the treatment of acromegaly and neuroendocrine tumors. Their biological effects are mediated via high affinity plasma membrane receptors that are found throughout the body and on many human tumors. Clinical studies show a reduction in serum IGF-1 and IGF-1 gene expression after treatment with octreotide (1). Somatostatin and analogs also enhance secretion and expression of IGF-binding protein-1, which negatively regulates plasma IGF-1, while inhibiting mitogens and secretion of gastrointestinal hormones implicated in tumor growth. Somatostatin analogs also show immune-modulating activity in vitro and inhibit angiogenesis and directly induce cell growth arrest and apoptosis in vivo and in vitro (7).

Melatonin is a free-radical scavenger and displays anti-proliferative effects on various cancer cell lines in vitro, but no human studies show evidence of anti-tumor activity. Melatonin shows antimyelodysplastic activity and reduces bone marrow toxicity of chemotherapeutic agents in animal models. See melatonin for additional information (2)(3)(4)(5).

Bromocriptine is a dopamine agonist and prolactin inhibitor. Prolactin stimulates growth of lymphomas in vivo and in vitro, and prolactin receptors are present on normal and neoplastic lymphoid cells.

Retinoids act as antioxidants and immunostimulants, cause cell growth arrest in B-cell lymphomas in vitro, and have shown benefit in trials of promyelotic leukemia and cutaneous T-cell lymphoma.

ACTH receptors can be found on T and B lymphocytes and ACTH has been seen to depress lymphocyte blastogenesis and modulate NK cell activity in vitro (6).

Reported (DBM): Increased pain at tumor site in advanced cancer patients; somnolence, diarrhea, nausea, vomiting, anorexia, grade I hyperglycemia, ankle-feet edema; anemia and thrombocytopenia were noted in trials using cyclophosphamide (12).
Case Report (DBM): A breast cancer patient with lung and liver metastases developed acute myeloid leukemia, which her physicians associate with chronic cyclophosphamide use, after treatment with Di Bella therapy. Her leukemia led rapidly to death due to cerebral hemorrhage (13).
Common (Somatostatin): Gastrointestinal complaints (diarrhea, vomiting, and nausea), cholelithiasis, and effects on glucose metabolism (6).
Toxicity (Somatostatin): Pain at injection site, allergic reactions, hair loss, a few cases of reversible hepatic dysfunction (11).
Reported (Bromocriptine): Hypotension, peripheral vasoconstriction, dyskinesias, fatigue, nausea, vomiting, postpartum MI, headache, dizziness, psychosis (6).
Reported (Melatonin): Drowsiness, alterations in sleep patterns, altered mental status, disorientation, tachycardia, flushing, pruritus, abdominal cramps, headache, hypothermia (6)(8)(14)(15).

Opiates: Somatostatin has opioid antagonist properties and has been observed to decrease or eliminate the analgesic effects of methadone and morphine in advanced cancer patients requiring pain relief (11).
Immunosuppressants (e.g., Cyclosporine, Tacrolimus): Bromocriptine is thought to inhibit the cytochrome P450IIIA isoenzyme family and reduce the metabolism of drugs such as cyclosporine and tacrolimus, increasing the risk of toxicity from these medications.
Macrolides: Potentiate adverse effects of bromocriptine.
Efavirenz: Increases the effect of bromocriptine.
Protease inhibitors: Bromocriptine may potentiate their effect.
Anti-hypertension drugs: Bromocriptine may have an added hypotensive effect.
Bromocriptine is inhibited by drugs that increase prolactin concentration (e.g., amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine) (17).
Nifedipine: Concomitant administration of melatonin and nifedipine has resulted in elevations in blood pressure and heart rate (16).
Fluvoxamine: Fluvoxamine may increase circulating plasma levels of melatonin resulting in sedation (9).
Succinylcholine: Cyclophosphamide potentiates the effect of succinylcholine.
Digoxin: Cyclophosphamide decreases the effect of digoxin.
St. Johns Wort: May decrease the effect of cyclophosphamide.


  1. Bousquet C, at al. Antiproliferative effects of somatostatin and analogs. Chemotherapy 2001;47(suppl 2):30-9.

  2. Cos S, Garcia-Bolado A, Sanchez-Barcelo EJ. Direct antiproliferative effects of melatonin on two metastatic cell sublines of mouse melanoma (B18BL6 and PG19). Melanoma Res 2001;11:197-201.

  3. Scarpignato C, Pelosini I. Somatostatin analogs for cancer treatment and diagnosis: an overview. Chemotherapy 2001;47(suppl 2):1-29.

  4. Sack RL, Lewy AJ, Hughes RJ. Use of melatonin for sleep and circadian rhythm disorders. Ann Med 1998;30:115-21.

  5. Hartter S, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.

  6. DeMuro RL, et al. The absolute bioavailability of oral melatonin. J Clin Pharmacol 2000;40:781-4.

  7. Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med 1998:30:122-30.

  8. Brzezinski A. Melatonin in humans. N Engl J Med 1997;336:186-95.

  9. Remuzzi G, Schieppati A. Lessons from the Di Bella affair. Lancet 1999;353:1289-90.

  10. Simini B. Somatostatin fever mounts in Italy. Lancet 1998;351:428.

  11. Italian Study Group for the Di Bella Multitherapy Trials. Evaluation of an unconventional cancer treatment (the Di Bella multitherapy): results of phase II trials in Italy. BMJ 1999;318:224-8.

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