The frequency of administration of zolendronic acid can be safely reduced by 67% in patients suffering from breast cancer with bone metastases. Clinical studies have shown that reducing dosages leads to a reduction in serious side effects of the drug, such as osteonecrosis of the mandible and renal toxicity.
The frequency of administration of zolendronic acid can be safely reduced by 67% in patients suffering from breast cancer with bone metastases. The data from the Phase III clinical trial presented at the 2014 ASCO Annual Symposium convincingly showed that reducing dosages leads to a reduction in serious side effects of zolendronic acid, such as osteonecrosis of the mandible and renal toxicity.
Zolendronic acid, being a nitrogen-containing bisphosphonate of the 3rd generation, reduces the severity of clinical manifestations of bone metastases. The standard mode of administration of the drug is 4 mg intravenously every 3-4 weeks for the 1st year. The optimal duration of the treatment regimen has not yet been presented. However, long-term monthly use of zolendronic acid (more than 3 years) It can lead to serious complications such as osteonecrosis of the jaw and chronic renal failure.
The double-blind multicenter phase III OPTIMIZE-2 study included 403 breast cancer patients (mean age 59 years) with bone metastases who were treated with intravenous bisphosphonates for 10 to 15 months. The patients continued treatment with zolendronic acid monthly (200 patients) or every 3 months (203 patients) for 1 year. Neither the researcher nor the patient could know what specific treatment they were receiving: the women in the control group were given a placebo. The characteristics of the patients were identical in both groups.
The result was the ratio of skeleton-related events (CVD), defined as the ratio of patients with ≥1 CVD (i.e., pathological fracture, spinal cord compression, with the need for radiation therapy or orthopedic intervention). The term "noninferiority" was specifically introduced, i.e. "no deterioration" when prescribing zolendronic acid with an extended interval compared to standard treatment. At the same time, the time before the onset of CVD, the dynamics of bone markers were studied, pain was assessed on a pain scale and the safety of the prescribed treatment.
The results were presented at a median follow-up of 11.9 months. At the same time, the primary point of the study was achieved: the results of prescribing zolendronic acid once every 12 weeks were no worse than the monthly regimen. The differences were 1.2% in CCC ratio (95% CI, 7.5%-9.8%; P = .724), at 22% (n = 44) and 23.2% (n = 47) in the first and second observation groups, respectively.
Secondary goals were also comparable between the two groups. The time to the onset of the first CVD (HR = 1.06; 95% CI, 0.70-1.60; P = .792) and the deviations in bone remodeling markers were also identical.
The toxicity profiles were also comparable between the two groups, with side effects occurring equally frequently.Grade 3-4 toxicity was described in 47.5% (n = 94) and 42.6% (n = 86) of the follow-up groups, respectively. The severity of pain and the need for painkillers did not vary in the groups.
A less intensive bisphosphonate regimen minimized the incidence of serious side effects, such as osteonecrosis of the mandible, to 0. Renal toxicity was also lower in this mode, 7.9% (n = 16) versus 9.6% (n = 19)
A less intensive bisphosphonate regimen minimized the incidence of serious side effects, such as osteonecrosis of the mandible, to 0. Renal toxicity was also lower in this mode, 7.9% (n = 16) versus 9.6% (n = 19)
Thus, after 9-12 months of monthly administration of intravenous nitrogen-containing bisphosphonates, it is advisable to continue their administration once every 12 weeks. This does not lead to a decrease in the effectiveness of treatment of metastatic bone disease in breast cancer in women, while increasing the psychological comfort of patients and, importantly, reducing the cost of drug treatment for this complex category of patients
The OPTIMIZE-2 study was sponsored by Novartis, the manufacturer of zolendronic acid.
Hortobagyi GN, et al. ASCO 2014. Abstract LBA9500
BP, bisphosphonate; IV, intravenous; q4w, every 4 weeks; q12w, every 12 weeks; SRE, skeletal-related events. AE, adverse event; ONJ, osteonecrosis of the jaw; q4w, every 4 weeks; q12w, every 12 weeks; SD, standard deviation.
Was this information helpful?
Questions and answers
Lump in my breast
I have noted the lump in my breast periodically appeared following breastfeeding my first child (as a result of plugged duct). I did an ultrasound, but it revealed nothing, as if everything was normal. I knead my breast periodically and feel pain at those moments. Now I am pregnant, due date is on 20th. What should I
do?? When to examine my breasts, is it possible to perform the examination during pregnancy and lactation?
...more The "lump" in the breast cannot occur after feeding, even if it was the plugged duct. You should not "knead" the breasts. If there is a problem or even if you think it is – the breast should be examined. Pregnancy and breastfeeding are not contraindications for this. Under normal conditions for pregnant women we
recommend a breast examination during 1 and 3 trimester (before childbirth). There are no contraindications for breast examination in your case. You are welcome at any convenient time for examination and advice on breastfeeding.
...more
Benign disease
I have a benign lump in one breast size of 12.0*9.9 mm. Puncture or a biopsy will be done next week. I was told by mammologist that surgery is needed. As far as I know, concerning the surgery, axillary lymph nodes are to be removed together with the tumor. I also know that in Europe lymph nodes are testes for
specific markers and only affected ones should be removed; if lymph nodes are no affected, they are not to be dissected and the surgery is minimally invasive. So what is your approach? Does it make sense to do it or you have the same methods and the same equipment?
...more If histological examination of the sample reveals fibroadenoma of basic type or tissue hyperplasia without atypia, or nodular type fibrocystic condition of the breast tissue, the question of surgical treatment should not arise. If biopsy reveals giant fibroadenoma sectoral resection is indicated, i.e. mass excision
within the healthy tissues and lymph nodes will be removed. In case of non- benign histological result, i.e. carcinoma is detected, subsequent immunohistochemical examination is required as well as a clinical oncologist and surgeon consultation; and the decision on complex treatment will be taken by case management team. With regard to the diagnosis and treatment methods in our center, each case is addressed individually. Sometimes we remove a benign area (for example, the area of hyperplasia with atypia) using the vacuum-needle technique through 3-4 mm incision. As for the surgical procedure protocols for benign breast tumors, benign simple fibroadenoma is not removed in America, Europe, Israel, etc. I would like to discuss your case with you in more details and perform some additional tests if needed, so I would be glad to see you at EMC’s Breast center.
...more
Melanoma
My mom had a mole (suspected for melanoma) removed in November 2015. Histology revealed lentigo melanoma in situ. We checked the slides back in the Netherlands, and the diagnosis was a superficial spreading melanoma of Clark 3 Т1а Beslow 0,8 stage; re-excision with capture of 1 cm of healthy skin is recommended. Is
it possible to make re-excision and subsequent histology in your hospital? If so, how soon?
...more We absolutely agree with the opinion of the European colleagues: re-excision with a wider offset is required; according to the Russian Protocol it is necessary to move 2 cm from the peripheral edge. This is for counter insurance, as lentigo-melanoma is a favorable type, and previous surgery is likely to put an end to
this story and the forecast is favorable. All the necessary manipulations for the study are possible in our Clinic; we have our own well-equipped laboratory with the possibility to ask the advice concerning the sample in Germany and Israel.
You should make an appointment with the surgeon-oncologist (Marina Bissessar) in the nearest time to conduct the diagnostic re-excision. Hope to help!
...more
A spot on the back and chest
I have a spot on the back and chest, what could it be?
A spot on the skin is one of the most common symptoms of various skin diseases. Infectious (viral, bacterial or fungal) as well as noninfectious skin including serious diseases and nevi (moles or birthmarks) can manifest as spots on the skin. You should go to the dermatologist for accurate diagnosis. The doctor will
examine you and, if necessary, a special instrument (Dermatoscope, wood lamp) will be used. A skin scraping can also be done in the lesion for microscopy, cytology or culture. A treatment will be prescribed after diagnosis.
...more 
Batkaeva Nadezhda
07 September 2016
Uterine cancer
My mom was diagnosed with the uterine cancer. She is 68 years of age and has an obesity of 4th grade (the growth of 166 cm, weight 135 kg) and hypertension. Admission to the radiology department was recommended. What should we do? As far as I know the surgery is the only method for cancer of the uterus to be removed.
Is it really so that this surgery is only possible for young and relatively healthy persons?
...more It is not quite so. We can operate on any patient, but the issue is which complications can lead to patient’s death and which of them can just delay the recovery. From the anesthesiologist’s point of view, it is a major challenge to intubate patients with 4th degree obesity; the abdominal section is also possible,
but there is a 100% risk of suture line disruption and inflammation, let alone the postoperative pneumonia, venous thrombosis, etc. There is another option such as vaginal hysterectomy which is more acceptable and relatively safe in obese patients. It is not a «treatment standard», however, as it allows not obtaining pelvic washings, but still there is a possibility of complete cure. Anesthesia remains a problem - both general and spinal. Radiation therapy without surgery is another acceptable treatment option besides vaginal hysterectomy. A chance of complete cure is still exists, but the survival rate is on average lower than in surgical treatment
...more 
Vladimir Nosov
07 September 2016
.webp)
.webp)
.webp)
.webp)
