In uno studio  inglese  ,  presentato a Chicago ,  che confronta  CLODRONATO  1600 mg  per bocca  e ZOLENDRONATO 4 mg ev ogni 4 settimane

la sopravvivenza  mediana passa da 45 mesi a 50 mesi

 gli eventi critici ( fratture ossee in particolare) calano dal 35% nel primo caso al 27% con lo zoledronato

 

 fonte : medscape.com

 

 

June 16, 2010 (Chicago, Illinois) — In patients with multiple myeloma who have bone metastases or bone lesions, bisphosphonates are used as a standard of care to reduce the risk for skeletal-related events. But a new trial comparing 2 bisphosphonates in this setting has found that zolendronic acid also improved overall survival, compared with clodronate.

This survival benefit appeared to be independent of the effect of the drug on skeletal-related-events prevention, suggesting that zolendronic acid improves survival through anticancer activity, say the researchers, who presented their findings here at the American Society of Clinical Oncology 2010 Annual Meeting last week and at the European Hematological Association meeting in Barcelona this week.

There have been previous reports of zolendronic acid having anticancer activity, such as in breast cancer, as previously reported by Medscape Oncology.

This is the first time this effect has been seen clinically in myeloma, said Jean-Luc Harousseau, MD, from the Center for Research on Myeloma in Nantes, France, who discussed the trial at a Highlights of the Day session at the ASCO meeting.

As expected, zolendronic acid was shown to be the better drug at preventing and delaying skeletal-related events, he said. But it also showed a statistically significant 16% reduction in the risk for death, compared with clodronate (with a 5.5 month difference in median overall survival), he pointed out.

The new data come from the Myeloma IX study, funded by the Medical Research Council in the United Kingdom. It involved 1960 patients with newly diagnosed multiple myeloma, of whom about 70% had bone involvement, reported lead investigator Gareth Morgan, PhD, FRCP, from the Royal Marsden Hospital in London, United Kingdom.

All patients received first-line induction chemotherapy, although the extent of this treatment was guided by their status. The younger and/or fitter patients received intensive high-dose chemotherapy with stem cell support where appropriate; the older and/or less fit patients received standard chemotherapy.

At the same time, patients were randomized to receive 1 of 2 bisphosphonates: intravenous zolendronic acid 4 mg every 3 to 4 weeks, or oral clodronate 1600 mg daily. Patients remained on this treatment until at least disease progression, and just over 10% of patients remain on bisphosphonate therapy, Dr. Morgan said.

Median follow-up was 3.7 years.

Zolendronic acid was significantly better than clodronate in preventing skeletal-related events (seen in 27% vs 35.3% of patients, respectively; P = .0004). To give some perspective on this, Dr. Morgan noted that without bisphosphonate therapy, these events occur in about 50% of patients.

In addition, zolendronic acid significantly reduced the risk for death by 16%, and improved median overall survival to 50 months, compared with 44.5 months with clodronate (P = .0118). It also significantly improved progression-free survival (19.5 vs 17.5 months; P = .0179).

"Of note, the overall survival benefit was maintained after adjustment for the potential effects of skeletal-related events on survival," Dr. Morgan said, "so this does seem to be an antimyeloma effect."

Both bisphosphonates were generally well tolerated, and the deterioration in renal function was similar in both treatment groups, he said. Acute renal failure was reported in 5.2% to 6.5% of patients receiving the zolendronic acid and in 5.9% to 6.4% of those receiving clodronate. The incidence of confirmed osteonecrosis of the jaw was also low and the cases were generally mild, he added, although it was higher with zolendronic acid than with clodronate (3.5% vs 0.3% of patients).

Noting that there have been data from other clinical trials that have suggested an anticancer effect, Dr. Morgan concluded: "These data further support the anticancer activity of zolendronic acid, and provide evidence that zolendronic acid should be considered for the early integration into treatment regimens in patients with newly diagnosed multiple myeloma."

               

                                               

                                                    la struttura ossea al microscopio