Zometa = Zoledronic Acid geeft in dosis 4 mg. intraveneus gegeven volgens gerandomiseerde fase III studie (ruim 1600 patiënten) significant beter effect bij botproblemen dan APD - pamidronate 90 mg. bij borstkanker. Update 22 febr. 2010

Update 22 februari 2010: Al in 2004 bewees een grote fase III studie (zie hieronder) dat Zometa - Zoledronic Acid een beter effect geeft bij met name borstkankerpatienten dan APD - Pamidronate. De afgelopen jaren hebben we vele mensen hierop, gewezen maar slechts een enkeling kreeg Zometa - Zoledronic Acid voorgeschreven en zij nkregen het vaak niet eens vergoed. Lees nu in apart artikel hoe u Zometa wel voorgeschreven kunt krijgen en ook gewoon vergoed en hoe u Zometa thuis kunt krijgen toegediend. Klik hier hoe u Zometa thuis kunt krijgen toegediend en hoe u dit gewoon vergoed kunt krijgen via een speciaal formulier.

d.d. 8 januari 2004: Bron: Pumed en Medscape en verschillende studies achter elkaar gezet.

Een grote gerandomiseerde fase III studie (1600 patiënten zijn 25 maanden gevolgd) heeft uitgewezen dat Zometa = Zoledronic Acid in een dosis van 4 mg. intraveneus significant beter resultaten geeft ten opzichte van 90 mg. dosis Pamidronate (APD) ter voorkoming en herstel van botontkalking bij patiënten met borstkanker en gelijk aan effect bij patiënten met MM - Multiple Myeloma (Kahler).

Citaat uit studierapport:
In patients with breast carcinoma, zoledronic acid (4 mg) was significantly more effective than pamidronate, reducing the risk of SREs by an additional 20% (P = 0.025) compared with pamidronate and by an additional 30% in patients receiving hormonal therapy (P = 0.009).

Belangrijk is te weten dat bij chemo en het toenemende gebruik van aromaseremmers de botontkalking vaak een probleem is en met deze aanvullende middelen kunnen problemen hiermee worden tegen gegaan. Lees meer over bisfosfonaten op borstkanker en clodronate. en borstkanker en Bondronat.

Bron: Pubmed en andere medische website's zoals Medscape: eerst een interview met een professor oncologie over deze studie en daaronder een abstract van de studie:

Narrator: In a large, randomized study of more than 1,600 patients, 4 mg of zoledronic acid compared favorably to the standard 90-mg dose of pamidronate for the treatment of bone lesions secondary to advanced breast cancer or multiple myeloma. However, zoledronic acid was more effective than pamidronate in lowering the risk of multiple skeletal events, especially for patients with advanced breast cancer. The study findings are available in the October issue of the journal Cancer.

Dr. Julie Gralow, associate professor of Medical Oncology at the University of Washington School of Medicine and Fred Hutchinson Cancer Research Center in Seattle, Washington, said the study was designed to show the non-inferiority of zoledronic acid compared to pamidronate, which was the standard of care at the time the study began.

Dr. Gralow: For the group as a whole, as well as if you broke out the breast cancer patients or the myeloma patients, they appeared to be quite equivalent if you looked at, for example, the number of skeletal-related events that occurred, the time to the first skeletal-related event, and other factors like that.

Narrator: In the study, patients were randomized in a double-blind fashion to receive 4 or 8 mg of zoledronic acid or 90 mg of pamidronate. Because of concerns over renal toxicity, the 8 mg dose of zoledronic acid was reduced to 4 mg during the trial, and the infusion time was lengthened from five minutes to 15 minutes. Patients who originally received the 8-mg dose were not included in the efficacy analysis.

All patients received daily oral vitamin D and calcium, had good performance status, and were on antineoplastic or hormonal therapy at the time of randomization. None had received bisphosphonates in the 12 months prior to a screening visit. About 70% of the patients in the efficacy analysis had breast cancer. This 25-month study was an extension of a previous study.

The study investigators, led by Dr. Lee Rosen, director of Developmental Therapeutics at the Cancer Institute Medical Group in Santa Monica, California, used the Andersen-Gill multiple event analysis to evaluate the risk of multiple skeletal-related events. Dr. Gralow explains Andersen-Gill is a sensitive method for taking into account the number of events as well as the time between events.

Dr. Gralow: In this case, the zoledronate appears to be a winner. There's about a 20% reduction in this multiple event analysis scoring with zoledronate versus pamidronate, and it is statistically significant. I think that it suggests that zoledronic acid has some superiority possible when we look at number of events, time to first events all factored together, in addition to being just simply far more convenient to infuse.

Narrator: Dr. Gralow, who specializes in the treatment of breast cancer, says that skeletal-related events secondary to the disease are not the only bone health concern in women with advanced breast cancer. Hormone therapy with, for example, aromatase inhibitors, puts women with breast cancer at risk for bone loss.

Dr. Gralow: The aromatase inhibitors are associated with increased bone loss. So I think as we use aromatase inhibitors more and more, earlier and earlier, maybe even looking at it in the prevention setting, we're going to have to pay particular attention to bone loss. After all, we're hoping that these patients will survive their breast cancer, so that we do have to worry about osteoporotic fractures down the line.

Narrator: Likewise, Dr. Gralow emphasizes the importance of supportive care for women with advanced breast cancer. While bisphosphonate therapy may not extend survival, it can improve a patient's quality of life.

Dr. Gralow: And clearly, that's where the bisphosphonates come in for our patients with bone mets. If we can prevent or delay a skeletal-related event like a fracture or a cord compression or pain, then we've done them a great service. So I think it's critical that we provide supportive types of therapies, such as the bisphosphonates, in our bone metastases patients so that we can improve their quality of life.

Narrator: Because zoledronic acid is infused over 15 minutes, patients and staff find it much more convenient than pamidronate, which has to be infused over 2 hours.

Dr. Gralow: Obviously, that's a huge time for a metastatic patient if they're coming in every three to four weeks for one of these agents. I personally think that the less time spent in the chemo room and the more time spent with the family and at home, the better. So I view it as a big convenience thing, and a lot of my patients do, too.

In the metastatic setting we've got newer, more potent bisphosphonates that potentially can offer better quality of life for our patients, fewer fractures, longer time to first fracture. In the adjuvant setting, we've got the potential for preserving bone density. We have to sort this all out, make sure that we're, in the long run, not just preserving bone density but preserving bone quality. And we're also looking at bisphosphonates for preventing bone mets in the first place. That's the subject of clinical trials, but they're very interesting ongoing trials.

Narrator: For PeerView Press, I'm Dan Keller.
Resident Medical Review
Aman Shah, MBBS
Medical Director

PeerView Press is an independent, professional medical publishing concern focused on gathering and reporting information pertaining to clinically relevant advances and developments in the science and practice of medicine. PeerView Press is solely responsible for the selection of publication topics, the preparation of editorial content and the distribution of all materials it publishes. The preparation of PeerView reports is supported by educational grants subject to written agreements that clearly stipulate and enforce the editorial independence of PeerView Press. Our reports may contain references to unapproved products or uses of these products in certain jurisdictions. For approved prescribing information, please consult the manufacturer's product labeling. No endorsement of unapproved products or uses is made or implied by coverage of these products or uses in our reports. No responsibility is taken for errors or omissions in reports. The production of this report was supported by an unrestricted educational grant from Novartis Oncology.

Cancer. 2003 Oct 15;98(8):1735-44.

Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial.

Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein MA, Coleman RE, Reitsma DJ, Chen BL, Seaman JJ.

Developmental Therapeutics, Cancer Institute Medical Group, Santa Monica, California 90095, USA. RosenL@jwci.org

BACKGROUND: The goal of the current study was to compare the long-term (25-month) safety and efficacy of zoledronic acid with pamidronate in patients with bone lesions secondary to advanced breast carcinoma or multiple myeloma.

METHODS: Patients (n = 1648) were randomized to receive 4 mg or 8 mg (reduced to 4 mg) zoledronic acid as a 15-minute infusion or to receive 90 mg pamidronate as a 2-hour infusion every 3-4 weeks for 24 months. The primary endpoint was the proportion of patients with at least 1 skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate, and multiple-event analysis. Hypercalcemia of malignancy (HCM) was included as an SRE in some secondary analyses.

RESULTS: After 25 months of follow-up, zoledronic acid reduced the overall proportion of patients with an SRE and reduced the skeletal morbidity rate similar to pamidronate. Compared with pamidronate, zoledronic acid (4 mg) reduced the overall risk of developing skeletal complications (including HCM) by an additional 16% (P = 0.030). In patients with breast carcinoma, zoledronic acid (4 mg) was significantly more effective than pamidronate, reducing the risk of SREs by an additional 20% (P = 0.025) compared with pamidronate and by an additional 30% in patients receiving hormonal therapy (P = 0.009). Zoledronic acid (4 mg) and pamidronate were tolerated equally well. The most common adverse events included bone pain, nausea, and fatigue.

CONCLUSIONS: Long-term follow-up data confirm that zoledronic acid was more effective than pamidronate in reducing the risk of skeletal complications in patients with bone metastases from breast carcinoma and was of similar efficacy in patients with multiple myeloma. Copyright 2003 American Cancer Society.

PMID: 14534891 [PubMed - indexed for MEDLINE]

J Clin Oncol. 2001 Jan 15;19(2):558-67.

Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials.

Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, Yunus F, Bell R, Body J, Quebe-Fehling E, Seaman J.

Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada. pierre.major@hrcc.on.ca

PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium > or = 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate-treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively. CONCLUSION: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.

PMID: 11208851 [PubMed - indexed for MEDLINE]