DiBella Therapy Was Worthless

Gianfilippo Bertelli, M.D.

The so-called Di Bella therapy is an unorthodox cancer treatment which was at the center of a collective hysteria in Italy for several months during 1997 and 1998. The treatment is named after its proponent, Professor Luigi Di Bella (1912-2003), a retired physiologist who lived in Modena. It is based on a combination of somatostatin, vitamins, retinoids, melatonin, and bromocriptine. ACTH (adrenocorticotropic hormone) and low oral doses of the well-known chemotherapeutic agents cyclophosphamide and hydroxyurea are sometimes also included. Di Bella claimed that his treatment stimulates the body's self-healing properties without damaging healthy cells. However, he provided no supportive experimental evidence, and—despite his claims to have cured thousands of patients with a variety of cancers—never documented his clinical results in a peer-reviewed scientific journal. Silvio Garattini, a respected pharmacologist who heads the Mario Negri Institute in Milan, has described Di Bella's regimen as a "totally irrational association of drugs supported by absolutely no scientific evidence or data whatsoever." [1]

Di Bella was born in the Sicilian village of Linguaglossa, the 13th child of a clerical worker. He studied medicine at Bari University, served as a wartime army doctor in Greece, and became professor of physiology at Modena University in 1948 [2]. In December 1997, he made headlines after Carlo Madaro, a judge in the Southern Italy city of Maglie, ruled that the health authority should fund the treatment for a patient. The case involved a 2-year-old child with brain cancer who was being treated with Di Bella's regimen. The child's parents asked for free somatostatin, believed to be the regimen's key component. Under Italian law, somatostatin and its analogue octreotide can only be prescribed to manage the diarrhea and flushing associated with rare tumors called carcinoids. Despite this, most pharmacies in Italy had run out of these costly drugs because of the Di Bella regimen's popularity, and many patients were buying them abroad. After judges in several more Italian towns backed the requests of patients asking for somatostatin, a Lancet editorialist commented: "It is unfortunate that the judiciary has the power to sweep aside carefully constructed prescribing plans on the basis of little clinical opinion." [3].

The child died of cancer in July 1998. Meanwhile, however, public interest in the unconventional treatment mounted to an unprecedented high—even for a country where "miracle cancer cure" proponents emerge periodically. Cancer patients supporting Di Bella organized demonstrations in the streets with chants of "freedom of treatment." Magazines, newspapers, and television stations—especially those linked to right-wing opposition parties—expressed support. Many cancer patients abandoned conventional treatment modalities and asked to receive Di Bella's therapy, which supposedly had no toxic effects. Oncologists were accused of conspiring to keep cancer patients away from a potentially curative therapy. Political leaders were criticized, and rumors of a possible Government crisis began to spread. Then, following a televised debate with Di Bella in January 1998—watched by nine million Italians—Minister of Health Rosy Bindi announced that clinical trials would be carried out in public hospitals. Di Bella was asked to collaborate with the leading Italian cancer specialists in writing the trial protocols.

The decision, according to a Ministry of Health spokesperson, was made to resolve a "problem of public order." However, some cancer specialists were critical and refused to participate in the research, because they believed it was unethical and appeared to legitimise Di Bella's claims. The scientific journal Nature compared the Di Bella affair with that of laetrile in the United States during the 1970s and early 1980s [4]. During that period, despite lack of evidence of effectiveness, several states passed laws permitting laetrile to be prescribed; and public pressure led government agencies to permit a clinical trial, which proved negative [5].

Following Bindi's announcement, Italian hospitals were flooded by requests of cancer patients to be included in the clinical trials. The patients were screened at cancer centers by a cancer specialist and were given the option of conventional treatment. To be eligible for the Di Bella regimen, patients had to have easily measurable tumor masses and be in relatively good physical condition. Some eligible patients (some of whom had not previously seen a cancer specialist!) decided to undergo conventional treatment instead. Those who chose the Di Bella treatment were entered into nine phase II, open-label studies at several cancer centers. These studies included patients with cancers of the breast, lung, pancreas, colon, brain, head and neck, and non-Hodgkin lymphomas who were unresponsive to conventional treatments or who had refused proven treatments. Patients with more advanced cancers were eligible for another trial, an ill-defined study intended to follow a total of 2,600 patients.

Although the public expected to learn within a few months whether the Di Bella's regimen was superior to conventional treatments, warnings came out that the trials lacked control groups and could not provide conclusive evidence. Meanwhile, Di Bella himself expressed fears that the results would be "sabotaged" by mainstream doctors. He also accused drug companies of conspiring against him and even claimed he had been the target of an assassination attempt. The drama increased when Di Bella, speaking to European Parliament members, announced that his regimen is also effective against retinitis pigmentosa, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, all of which have no known medical cure.

Di Bella had boasted that his personal files contained proof that he had cured thousands of patients. In June, however, his credibility was shaken by an analysis of 3076 of his records. According to the National Institute of Health, 1,553 (50%) contained no documentation that the patient had cancer or lacked other essential information. Of the rest, 918 were excluded from further consideration because they lived in areas where tumor registries were not available, which meant that reliable survival information was not available. Out of 605 patients living in areas covered by local tumor registries, only 248 had sufficient documentation of diagnosis and treatments. However, 244 of them had also received conventional treatments, which meant that no favorable conclusion could be drawn.

Then, in early July, the first results of a clinical trial sponsored by the administration of the region Lombardy—with broader eligibility criteria than the trials carried on by the Ministry of Health—were released [6]. Out of 333 evaluable patients, only one (0.3%) showed a partial response, and one-third showed no change. Half the patients had local growth of their tumors, and 14% had new metastatic involvement. Adverse effects (nausea, vomiting, diarrhea, neurological signs) were reported in 23% of patients, and 3.3% had to stop because of adverse effects.At the end of July, further negative results were announced. Four of the State-sponsored trials had been concluded. Not a single one of the 136 enrolled patients had shown improvement. Only 9% had a stable disease during treatment, while 50% progressed, 25% died, and 13% abandoned the regimen because of adverse side effects. The other 3% were not available for evaluation. Although a poll found that 67% of Italian adults still had faith in Di Bella, the media seemed to have lost interest in the affair.

A final report tabulating the results among 386 patients as of October 31, 1998, found:

No patient showed complete remission. Three patients showed partial remission: 1 of the 32 patients with non-Hodgkin's lymphoma; 1 of the 33 patients with breast cancer; and 1 of the 29 patients with pancreatic cancer. At the second examination, 12% (47) of the patients had stable disease; 52% (199) progressed; and 25% (97) died.

Conclusion: DiBella multitherapy did not show sufficient efficacy in patients with advanced cancer to warrant further clinical testing [7].

As with other unorthodox cancer treatments, the controversy over Di Bella's therapy caused unnecessary suffering for patients and their families. Media fervor, judicial decisions, and public pressure compelled the government to sponsor clinical trials despite the lack of scientific evidence. Predictably, results were negative. The trials helped calm public hysteria and kept some cancer patients from abandoning effective treatments. This was achieved, however,with considerable waste of precious government resources.

References

  1. Anonymous. More clinical judgment, fewer 'clinical' judges. Lancet 351:303, 1998.
  2. Willan P. Obituary: Luigi di Bella. The Guardian, July 8, 2003.
  3. Simini B. Somatostatin fever mounts in Italy. Lancet 351:428, 1998.
  4. Abbott A. Controversial cancer drug wins local approval in Italy. Nature 391:217, 1998.
  5. Moertel C and others. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. New England Journal of Medicine 306:201­206, 1982.
  6. Simini B. Italian 'wonder' cure for cancer is ineffective. Lancet 352:207,1998.
  7. 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. British Medical Journal 318:224-228, 1999.

_________________

Dr. Bertelli is a medical oncologist at the National Institute for Cancer Research in Genoa, Italy. His opinions do not necessarily reflect those of the Institute.

The Italian League against Cancer, a nonprofit organization similar to the American Cancer Society, offers information (in Italian) about unproven cancer treatments, including the Di Bella regimen. Comments from abroad are welcome. If you would like a comment translated into Italian for posting, please send it directly to me.

Dott. Gianfilippo Bertelli
Oncologia Medica
Istituto Nazionale per la Ricerca sul Cancro Largo R. Benzi 10
16132 Genova
tel. 010/5600668 - fax 5600850
e-mail: bertelli@sos.unige.it

This article was revised on November 21, 2006.