Randomized, Placebo-Controlled Trial of Clodronate in Patients With Primary Operable Breast Cancer

2002 ◽  
Vol 20 (15) ◽  
pp. 3219-3224 ◽  
Author(s):  
Trevor Powles ◽  
Sandy Paterson ◽  
John A. Kanis ◽  
Eugene McCloskey ◽  
Sue Ashley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Controlled Trial ◽  
Multicenter Trial ◽  
Primary Treatment ◽  
Operable Breast Cancer ◽  
Double Blind ◽  
Intent To Treat ◽  
Primary Operable Breast Cancer

PURPOSE: The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases. PATIENTS AND METHODS: This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995. All patients received surgery, radiotherapy, chemotherapy, and tamoxifen as required. Patients were randomized to receive oral clodronate 1,600 mg/d or a placebo for 2 years starting within 6 months of primary treatment. The primary end point was relapse in bone, analyzed on an intent-to-treat basis, during the medication period and during the total follow-up period (median follow-up, 2,007 days). Secondary end points were relapse in other sites, mortality, and toxicity. RESULTS: During the total follow-up period, there was a nonsignificant reduction in occurrence of bone metastases (clodronate, n = 63; placebo, n = 80; hazards ratio [HR], 0.77; 95% confidence interval [CI], 0.56 to 1.08; P = .127). During the medication period there was a significant reduction in the occurrence of bone metastases (clodronate, n = 12; placebo, n = 28; HR, 0.44; 95% CI, 0.22 to 0.86; P = .016). The occurrence of nonosseous metastases was similar (clodronate, n = 112; placebo, n = 128; P = .257), but there was a significant reduction in mortality (clodronate, n = 98; placebo, n = 129; P = .047) during the total follow-up period. CONCLUSION: Clodronate, given to patients with primary operable breast cancer, may reduce the occurrence of bone metastases, although this reduction was only significant during this medication period. There was a significant reduction in mortality.

Adjuvant aminoglutethimide for postmenopausal patients with primary breast cancer: analysis at 8 years.

1992 ◽  
Vol 10 (10) ◽  
pp. 1547-1552 ◽  
Author(s):  
A L Jones ◽  
T J Powles ◽  
M Law ◽  
A Tidy ◽  
D Easton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Controlled Trial ◽  
Multicenter Trial ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Event Free Survival ◽  
Double Blind ◽  
Free Survival

PURPOSE The study purpose was to evaluate aminoglutethimide (AG) as adjuvant therapy in patients with primary node-positive breast cancer in a randomized double-blind placebo-controlled trial. PATIENTS AND METHODS In a multicenter trial, 354 postmenopausal women with early breast cancer and histologically confirmed positive axillary lymph nodes were randomized after surgery to received aminoplac. Patients were prescribed either AG 250 mg four times per day and hydrocortisone 20 mg twice per day or placebos of identical appearance for 2 years. RESULTS After a median follow-up of 8.1 years, there has been no overall benefit for AG in terms of either event-free survival or overall survival (OS). However, the results are consistent with interim analyses with a significantly improved event-free survival for patients who received AG for up to 4 years, although this benefit subsequently disappears. Similarly, there is an improved OS for patients who received AG for up to 4 years, but this also subsequently disappears. There was a marginal advantage for estrogen receptor (ER)-positive patients who received AG (n = 74; P = .054). There was no difference in the sites of relapse. There was a significant increase in toxicity for patients who received AG. CONCLUSION The lack of survival benefit with long-term follow-up for AG may indicate that aromatase inhibitors have less of an impact on early breast cancer than tamoxifen and may imply different biologic mechanisms of action.

Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.

1995 ◽  
Vol 13 (3) ◽  
pp. 547-552 ◽  
Author(s):  
T J Powles ◽  
T F Hickish ◽  
A Makris ◽  
S E Ashley ◽  
M E O'Brien ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Adjuvant Therapy ◽  
Randomized Trial ◽  
Response Rate ◽  
Neoadjuvant Treatment ◽  
Operable Breast Cancer ◽  
Chemoendocrine Therapy ◽  
Primary Operable Breast Cancer

PURPOSE To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.

Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.

1993 ◽  
Vol 11 (1) ◽  
pp. 59-65 ◽  
Author(s):  
A H Paterson ◽  
T J Powles ◽  
J A Kanis ◽  
E McCloskey ◽  
J Hanson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Bone Pain ◽  
Controlled Trial ◽  
Metastatic Breast ◽  
Spinal Pain ◽  
Recurrent Breast Cancer ◽  
Nonvertebral Fracture ◽  
Double Blind ◽  
Oral Clodronate

PURPOSE Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer. PATIENTS AND METHODS We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients). RESULTS The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups. CONCLUSIONS These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.

Bone metastases in primary operable breast cancer. The role of serial scintigraphy

1984 ◽  
Vol 20 (8) ◽  
pp. 1019-1023 ◽  
Author(s):  
Henrik S Thomsen ◽  
Jens Otto Lund ◽  
Ole Munck ◽  
Knud West Andersen ◽  
Mikael Støckel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Operable Breast Cancer ◽  
Primary Operable Breast Cancer

scholarly journals Routine tests during follow-up of patients after primary treatment for operable breast cancer

1995 ◽  
Vol 6 (8) ◽  
pp. 769-776 ◽  
Author(s):  
D. Crivellari ◽  
K.N. Price ◽  
M. Hagen ◽  
A. Goldhirsch ◽  
R.D. Gelber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Treatment ◽  
Operable Breast Cancer
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