Biomedical subjects

A Lipton

Publications and source records attributed to A Lipton.

At least 37 records · Page 2Linked to original sources

PubMed1999

Bisphosphonates in the treatment of malignant bone disease.

Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by products produced by tumors or indirectly through other nonmalignant cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Since these agents were shown effective in treating other diseases associated with increased bone resorption, including cancer-related hypercalcemia and Paget's disease of bone, studies have been initiated to explore the use of bisphosphonates in patients with osteolytic bone metastases. Recent large randomized double-blind studies show the efficacy of these agents in reducing skeletal complications in patients with bone metastases from both breast cancer and multiple myeloma.

Antineoplastic Agents↗

PubMed1999

Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group.

PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.

Adolescent↗

PubMed1999

Bisphosphonate treatment of lytic bone metastases.

Tumour-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by tumour products or indirectly through an influence on other cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Pamidronate is a second-generation amino-bisphosphonate that is a potent inhibitor of osteoclastic activity. In multiple myeloma, a phase III study has shown that the proportion of patients at the end of 21 months who had any skeletal event was significantly lower in the pamidronate group (38%) than in the placebo group (58%). The therapeutic benefit was independent of the type of antimyeloma chemotherapy. Patients who received pamidronate had significant decrease in bone pain and delayed deterioration in performance status and quality of life. Overall there was no survival advantage in patients who received pamidronate. In similar fashion, in 2 phase III breast cancer trials, patients who received pamidronate had fewer skeletal events, decrease in bone pain and analgesic use, and slower deterioration of performance status that in those patients receiving placebo. Again, there was no survival advantage in these patients. Recent studies suggest that the bisphosphonates clodronate can prevent the development of bone metastases in patients with breast cancer.

Bone Neoplasms↗

PubMed1998

Markers of bone resorption in patients treated with pamidronate.

Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorption. In cancer patients with bone metastases, NTX is more often elevated than either of the pyridinolines. Bisphosphonates inhibit osteoclasts and their treatment decreases skeletal complications of malignancy. The aim of this study was to correlate urinary PYD, DPD, and NTX levels with clinical events in patients receiving pamidronate. 25 cancer patients with lytic bone disease were treated with monthly pamidronate combined with endocrine or chemotherapy; 27 others were on placebo. Twenty-four hour urines were collected at baseline, 1, 3 and 6 months. NTX values were determined by enzyme-linked immunosorbent assay (ELISA); PYD and DPD values were determined by reverse phase high performance liquid chromatography (HPLC). Two hour urines were also collected weekly for 21 patients. The greatest difference as a result of pamidronate treatment was observed in NTX values. Maximum suppression was achieved 2 weeks after treatment. Of the 25 patients who received pamidronate, 21 had initially elevated NTX values. 12 of the 21 finished with normal NTX values, whilst 9/21 had NTX values which remained abnormally elevated. The proportions of patients with fractures between these two subgroups approached statistical significance (P = 0.07) while the proportions with bony disease progression were significant (P = 0.03, Fisher's exact test). Measuring NTX levels appears useful in monitoring bisphosphonate therapy of bone metastases. The goal of treatment should be to normalise NTX excretion.

Aged↗

PubMed1998

Pharmacology and clinical efficacy of bisphosphonates.

Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by products produced by tumors or indirectly through other nonmalignant cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Because these agents were shown to be effective in treating other diseases associated with increased bone resorption, including cancer-related hypercalcemia and Paget's disease of bone, studies were initiated to explore the use of bisphosphonates in patients with osteolytic bone metastases.

Bone Neoplasms↗

PubMed1998

Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group.

PURPOSE: To determine the efficacy and safety of 21 monthly cycles of pamidronate therapy in patients with advanced multiple myeloma. PATIENTS AND METHODS: Patients with stage III myeloma and at least one lytic lesion received either placebo or pamidronate 90 mg intravenously administered as a 4-hour infusion monthly for 21 cycles. At study entry, the patients were stratified according to whether they were to receive first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy. Skeletal events (pathologic fracture, radiation or surgery to bone, and spinal cord compression) and hypercalcemia were assessed monthly. RESULTS: The results of the first nine previously reported cycles are extended to 21 cycles. Of the 392 randomized patients, efficacy could be evaluated in 198 who received pamidronate and 179 who received placebo. After 21 cycles, the proportion of patients who developed any skeletal event was lower in the pamidronate-group (P = .015). The mean number of skeletal events per year was less in the pamidronate-group (1.3) than in placebo-treated patients (2.2; P = .008). Although survival was not different between the pamidronate-treated group and placebo patients overall, stratum 2 patients who received pamidronate lived longer than those who received placebo (14 v 21 months, P = .041). Pamidronate was safe and well tolerated during the 21 cycles of therapy. CONCLUSION: Long-term monthly infusions of pamidronate as an adjunct to chemotherapy are superior to chemotherapy alone in reducing skeletal events in stage III multiple myeloma patients, and may improve the survival of patients on salvage therapy.

Diphosphonates↗

PubMed1998

Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group.

PURPOSE: Pamidronate, an aminobisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years. PATIENTS AND METHODS: Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated. RESULTS: As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (i.e., vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group. The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long-term treatment did not result in any unexpected adverse events. Survival did not differ between the two groups. CONCLUSION: The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect was maintained for at least 2 years. Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer.

Alkaline Phosphatase↗

PubMed1998

Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment.

PURPOSE: To determine the toxicity, pharmacokinetics, response rate, and response duration of intravenous (i.v.) administration of recombinant, humanized anti-p185HER2 monoclonal antibody (rhuMAb HER2) plus cisplatin (CDDP) in a phase II, open-label, multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer. PATIENTS AND METHODS: The study population consisted of extensively pretreated advanced breast cancer patients with HER2/neu overexpression and disease progression during standard chemotherapy. Patients received a loading dose of rhuMAb HER2 (250 mg i.v.) on day 0, followed by weekly doses of 100 mg i.v. for 9 weeks. Patients received CDDP (75 mg/m2) on days 1, 29, and 57. RESULTS: Of 37 patients assessable for response, nine (24.3%) achieved a PR, nine (24.3%) had a minor response or stable disease, and disease progression occurred in 19 (51.3%). The median response duration was 5.3 months (range, 1.6-18). Grade III or IV toxicity was observed in 22 of 39 patients (56%). The toxicity profile reflected that expected from CDDP alone with the most common toxicities being cytopenias (n = 10), nausea/vomiting (n = 9), and asthenia (n = 5). Mean pharmacokinetic parameters of rhuMAb HER2 were unaltered by coadministration of CDDP. CONCLUSION: The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response rates higher than those reported previously for CDDP alone, or rhuMAb HER2 alone. In addition, the combination results in no apparent increase in toxicity. Finally, the pharmacology of rhuMAb HER2 was unaffected by coadministration with CDDP.

Adult↗

PubMed1998

Collagen cross-link excretion during space flight and bed rest.

Extended exposure to weightlessness results in bone loss. However, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion of PYD cross-links and N-telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab missions, as well as during short (14-day) and long (119-day) bed-rest studies. During space flight, the urinary cross-link excretion level was twice those observed before flight. Urinary excretion levels of the collagen breakdown products were also 40-50% higher, during short and long bed rest, than before. These results clearly show that the changes in bone metabolism associated with space flight involve increased resorption. The rate of response (i.e. within days to weeks) suggests that alterations in bone metabolism are an early effect of weightlessness. These studies are important for a better understanding of bone metabolism in space crews and in those who are bedridden.

Adult↗

PubMed1998

Aredia: the once-monthly infusion for the treatment of bone metastases.

Cancer cells produce a variety of cytokines that stimulate osteoclasts to resorb bone, leading to cancer-mediated destruction of the skeleton. Bisphosphonates, which are deposited on the surface of bone as a response to increased resorption, are potent inhibitors of this osleoclastic resorption. Several studies have suggested that bisphosphonate therapy can retard the formation of new bone metastases in patients with metastatic bone disease. First-generation bisphosphonates (etidronate and clodronate) were not suitable for long-term treatment and have now been superseded by second-generation bisphosphonates (pamidronate), which are more potent and do not have adverse effects on bone mineralization. Further generations of these drugs have now entered clinical trials.

Antineoplastic Agents↗

PubMed1998

Use of bisphosphonates in patients with metastatic bone disease.

Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by products produced by tumors or indirectly through other nonmalignant cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Since these agents had demonstrated efficacy in treating other diseases associated with increased bone resorption, including cancer-related hypercalcemia and Paget's disease of bone, studies were initiated to explore the use of bisphosphonates in patients with osteolytic bone metastases. Recent, large, randomized, double-blind studies have shown the efficacy of these agents in reducing skeletal complications in patients with bone metastases from both breast cancer and multiple myeloma.

Bone Neoplasms↗

PubMed1998

Detection of cancer cells in peripheral blood of breast cancer patients using reverse transcription-polymerase chain reaction for epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) has been reported to be expressed in high levels in primary breast cancer by immunohistochemistry. In the present study, a reverse transcription (RT)-PCR assay using EGFR primers was developed and evaluated for the detection of circulating micrometastases in the blood of breast cancer patients. Total RNA was extracted from breast cancer cell lines and from the blood of 23 control individuals and 37 breast cancer patients. After reverse transcription, outer and nested primers for EGFR were used for cDNA amplification. RNA integrity was confirmed with parallel RT-PCR amplification using beta2-microglobulin primers. PCR products were electrophoresed on agarose gels containing ethidium bromide and visualized by UV photography. Southern blotting was used to confirm EGFR specificity. The nested EGFR RT-PCR assay was capable of detecting a lower limit of 100 fg of total RNA from the A431 cell line. EGFR RNA was identified from the blood of 4 of 18 (22%) metastatic breast cancer patients, 0 of 6 locally recurrent breast cancer patients, 0 of 13 adjuvant breast cancer patients, and 0 of 23 controls (P = 0.03, metastatic versus control). The 18 metastatic breast cancer patients all had progressive disease at the time of blood sampling. The identity of the four EGFR-positive bands was confirmed by Southern blotting. The presence of RT-PCR positivity for EGFR was not a treatment-related phenomenon, because three of the four EGFR-positive patients were not receiving treatment at the time of blood collection. RT-PCR for EGFR is a sensitive and specific method for the detection of circulating micrometastases in a proportion of patients with metastatic breast cancer.

Biomarkers, Tumor↗

PubMed1997

Bisphosphonates and breast carcinoma.

The skeleton is a common site of breast carcinoma metastasis; 75% of patients with breast carcinoma demonstrate bone metastases at autopsy. The lytic destruction of bone in these patients is due to excessive osteoclastic activity. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Initial studies of breast carcinoma patients were performed with clodronate, a first-generation bisphosphonate. Studies with small cohorts suggested reduction of pain, analgesic requirement, and development of hypercalcemia. A larger randomized, double-blind, placebo-controlled trial of oral clodronate 1600 mg/day demonstrated a significant reduction of the combined rate of all morbid skeletal events (significant reduction of the incidence of vertebral fractures, rate of vertebral deformity, and hypercalcemic episodes). Trends were observed that favored clodronate for the treatment of nonvertebral fractures and radiotherapy for relief of bone pain. There was no survival difference between the clodronate and placebo groups (Paterson et al., J Clin Oncol 1993;11:59-65). Pamidronate is a second-generation aminobisphosphonate that is a much more potent inhibitor of osteoclastic activity. Phase II studies again suggested an improvement in many of the skeletal complications of breast carcinoma. Two large Phase III studies have recently been completed. Women with Stage IV breast carcinoma who were receiving cytotoxic chemotherapy (380 patients) or endocrine therapy (371 patients) and had at least 1 lytic bone lesion were given either pamidronate 90 mg as a 2-hour infusion monthly for 2 years or a placebo infusion. After the two studies were pooled, 367 patients treated with pamidronate and 384 patients given placebo were available for analysis. The median time to first complication (pathologic fracture, vertebral collapse, spinal cord compression, or treatment of bone with radiation or surgery) was 12.7 months for the pamidronate patients and 7.0 months for placebo patients (P = 0.001). The time to first fracture was 25.2 months for pamidronate patients and 12.8 months for placebo patients (P = 0.003). The proportion of patients with fracture was 40% for pamidronate vs. 52% for placebo (P = 0.002); the proportion with radiation administered to bone was 29% for pamidronate vs. 43% for placebo (P = 0.001); and the proportion with any skeletal event was 51% for pamidronate vs. 64% for placebo (P = 0.001). The skeletal morbidity rate (the number of complications per year) at 24 months was 2.4 for the pamidronate group and 3.7 for placebo (P = 0.001). Pain and analgesic use was decreased among the pamidronate patients. There was no difference in survival between the groups. Not all patients responded to the same dose of bisphosphonate. Recent data suggests that patients who have a normalization of their urinary excretion of N-telopeptide have a reduced risk of progression of disease in bone and fracture. In summary, the addition of pamidronate to standard chemotherapy or endocrine therapy produces a sustained reduction in skeletal complications in breast carcinoma patients with osteolytic bone metastases.

Bone Diseases↗

PubMed1997

Enhanced anti-proliferative activity of the combination of tamoxifen plus HER-2-neu antibody.

HER-2/neu overexpression has been associated with poor prognosis in human breast cancer. Many of these cancers are also ER-positive. A logical therapeutic approach for patients who are ER-positive and overexpress HER-2/neu may be to block both the ER and the HER-2/neu pathways. In our study, we used both the MTT tetrazolium dye assay and 3H-thymidine incorporation to measure the effects of the anti-estrogen Tamoxifen or the 4D5 anti-HER-2/neu antibody alone or in combination on the growth of BT474 human breast cancer cells which express ER and overexpress HER-2/neu. We found an enhanced inhibitory effect on cell proliferation with the combination of Tamoxifen and the antibody compared to that seen by either agent alone. This simultaneous interruption of both the ER and the HER-2/neu pathways may be relevant in the clinical treatment of patients who are both ER-positive and overexpress HER-2/neu.

Antibodies, Monoclonal↗

PubMed1997

Detection of mutant K-ras DNA in plasma or serum of patients with colorectal cancer.

Increased understanding of the molecular basis of colorectal cancer and recognition that extracellular DNA circulates in the plasma and serum of cancer patients enables new approaches to detection and monitoring. We used a polymerase chain reaction (PCR) assay to demonstrate mutant K-ras DNA in the plasma or serum of patients with colorectal cancer. Plasma or serum was fractionated from the blood of 31 patients with metastatic or unresected colorectal cancer and from 28 normal volunteers. DNA was extracted using either a sodium chloride or a gelatin precipitation method and then amplified in a two-stage PCR assay using selective restriction enzyme digestion to enrich for mutant K-ras DNA. Mutant K-ras DNA was detected in the plasma or serum of 12 (39%) patients, all confirmed by sequencing, but was not detected in any of the normal volunteers. K-ras mutations were detected in plasma or serum regardless of sex, primary tumour location, principal site of metastasis or proximity of chemotherapy and surgery to blood sampling. Tumour specimens available for 19 of the patients were additionally assayed for ras mutations and compared with blood specimens. Our results indicate mutant K-ras DNA is readily detectable by PCR in the plasma or serum of patients with advanced colorectal cancer. Thus, plasma- or serum-based nucleic acid amplification assays may provide a valuable method of monitoring and potentially detecting colorectal cancer.

Colorectal Neoplasms↗

PubMed1997

Phase I study combining tumor necrosis factor with interferon-alpha and interleukin-2.

We evaluated the effects of the addition of escalating doses of tumor necrosis factor (TNF) to two fixed doses and schedules of a combination of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) to determine the maximum tolerated dose of this three-cytokine combination and its feasibility as an outpatient regimen. Eighteen patients with metastatic cancer were enrolled. Each course consisted of 3 consecutive weeks of treatment with IFN-alpha 9 x 10(6) IU/m2/day intramuscularly (i.m.) or subcutaneously (s.c.) days 1, 3, and 5 each week for 3 weeks plus IL-2 continuous infusion 1 x 10(6) IU/m2/day (group A) or 3 x 10(6) IU/m2/day (group B) days 1-5 each week for 3 weeks. TNF was administered only during the first week of each course intravenously (i.v.) for 2 h on days 1-5. The dose of TNF was escalated (40, 80, 120 micrograms/m2) in cohorts of 3 patients. The most common side effects were fever, chills, and fatigue in all patients. Grade 3-4 toxicity included anemia (3 patients), thrombocytopenia (1 patients), arrhythmia (2 patients), pulmonary edema (3 patients),- and weight loss (1 patient). Five patients withdrew from study due to toxicity. The combination of the three cytokines is feasible as an outpatient regimen in one of the following combinations: (a) TNF 80 micrograms/m2/day as 2-h infusion on days 1-5 + IL-2 1 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks, or (b) TNF 40 micrograms/m2/day as a 2-h infusion on days 1-5 + IL-2 3 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks.

Adjuvants, Immunologic↗

PubMed1996

Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group.

BACKGROUND: Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone. METHODS: Women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion were given either placebo or pamidronate (90 mg) as a two-hour intravenous infusion monthly for 12 cycles. Skeletal complications, including pathologic fractures, the need for radiation to bone or bone surgery, spinal cord compression, and hypercalcemia (a serum calcium concentration above 12 mg per deciliter [3.0 mmol per liter] or elevated to any degree and requiring treatment), were assessed monthly. Bone pain, use of analgesic drugs, performance status, and quality of life were assessed throughout the trial. RESULTS: The efficacy of treatment was evaluated in 380 of 382 randomized patients, 185 receiving pamidronate and 195 receiving placebo. The median time to the occurrence of the first skeletal complication was greater in the pamidronate group than in the placebo group (13.1 vs. 7.0 months, P=0.005), and the proportion of patients in whom any skeletal complication occurred was lower (43 percent vs. 56 percent, P = 0.008). There was significantly less increase in bone pain (P=0.046) and deterioration of performance status (P=0.027) in the pamidronate group than in the placebo group. Pamidronate was well tolerated. CONCLUSIONS: Monthly infusions of pamidronate as a supplement to chemotherapy can protect against skeletal complications in women with stage IV breast cancer who have osteolytic bone metastases.

Antineoplastic Agents↗

PubMed1996

Fadrozole hydrochloride in postmenopausal patients with metastatic breast carcinoma.

BACKGROUND: Fadrozole hydrochloride (CGS-16949A) belongs to the class of aromatase inhibitors that lowers circulating estrogen levels by inhibiting the conversion of androgens to estrogens, thereby causing tumor regression in patients with breast carcinoma. METHODS: This was a prospective, randomized, Phase II study of fadrozole hydrochloride in postmenopausal patients with metastatic breast carcinoma. The three treatment groups received, respectively, fadrozole hydrochloride 0.6 mg three times daily, 1 mg twice daily, and 2 mg twice daily orally. RESULTS: Fifty-six patients were entered on protocol and 54 were eligible (2 patients were perimenopausal). Eight patients had received no prior therapy, 15 patients had received prior hormonal therapy, 5 patients had received prior chemotherapy, and 28 patients had received both. After 12 weeks of treatment, 2 complete and 3 partial responses were observed. Forty patients continued treatment beyond 12 weeks, and 3 additional responses were achieved. Thus, 8 of 56 patients responded (14% overall response rate). Responses did not appear to be dose-related. The median duration of response was 36 months (range, 8-45 months). Subjective toxicity was mild to moderate and appeared more frequent on the 2 mg twice daily dosing schedule. No objective toxicity in laboratory parameters was observed. No patient had severe or life-threatening toxicity. Fadrozole hydrochloride plasma concentrations (obtained every 2 weeks for 12 weeks) appeared to be dose-dependent and noncumulative. CONCLUSIONS: This study confirms modest activity of fadrozole hydrochloride in a heterogeneous group of patients with breast carcinoma treated at three different dose levels.

Adolescent↗