Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone appears to act like fertilizer for many tumors, including myeloma and metastatic breast cancer. The explanation must lie in interactions between tumor cells and the bone-tissue microenvironment. At this level, too, must lie the explanation of how bisphosphonates address not only cancer osteolysis but also the tumor burden. By inhibiting osteoclasts, the drugs may block a cancer-related vicious cycle.
 ...
PMID:Bisphosphonates as cancer drugs. 1034 36

(1) Pamidronic acid has no demonstrated influence on the survival time in patients with myeloma or bone metastases. (2) Two comparative placebo-controlled trials involving women with metastatic breast cancer show that a monthly infusion of pamidronic acid reduces the number of patients needing analgesic bone irradiation. It is not known whether pamidronic acid affects analgesic intake. (3) In myeloma, a placebo-controlled trial has shown that a monthly infusion of pamidronic acid reduces the number of patients requiring analgesic bone irradiation. Pamidronic acid also reduces analgesic use and the number of pathological fractures. (4) Overall, in the two indications, pamidronic acid reduces the frequency of all bone events, and postpones those that occur. (5) Pamidronic acid seems to be well tolerated. The most frequent adverse effect is fever after infusion.
 ...
PMID:Intravenous pamidronic acid: new indications. Useful palliative treatment for osteolysis. 1034 45

The demonstration of a dose-effect relationship in a wide spectrum of malignancies including solid tumors and lymphoproliferative disorders, along with the development of new techniques of hematopoietic stem cell support, have given rise to a growing interest for high-dose chemotherapy in recent years. Results in more than 3,000 patients included in nonrandomized trials have been reported in the literature. However, only nine randomized trials addressing the issue of the impact of high-dose chemotherapy on survival have been published: three in non-Hodgkin's lymphoma, one in multiple myeloma, two in metastatic breast cancer, one in germ-cell tumors, one in melanoma, and one in small-cell lung cancer. Firm, reliable conclusions can only be drawn from studies conducted in the salvage treatment of non-Hodgkin's lymphoma and in the first-line treatment of multiple myeloma: high-dose chemotherapy used in a consolidation setting after conventional chemotherapy leads to a survival advantage in chemosensitive patients. Promising but not firmly conclusive results were reported in metastatic breast cancer. The results of the sixteen ongoing randomized trials as well as studies addressing the issue of cost-effectiveness will be critical in establishing definite conclusions on the role of high-dose chemotherapy. With the exception of multiple myeloma and relapsed non-Hodgkin's lymphoma, there is no evidence for treating patients with high-dose chemotherapy outside randomized clinical trials.
 ...
PMID:High-Dose Chemotherapy in Adult Solid Tumors and Lymphoproliferative Disorders: The Need for Randomized Trials. 1038 35

Metastatic tumor cells can interfere directly with the function of bone cells involved in normal bone remodeling or indirectly by influencing the behavior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tumor cells interact closely with vascular endothelial cells, basement membrane and bone marrow stromal cells through cell surface proteins or by releasing factors which affect the function of these cells. Bidirectional interaction between marrow cells and tumor cells can give the latter a selective advantage for growth in bone which can lead to the destruction of or to increased production of bone matrix. Understanding of the mechanisms involved in tumor metastasis and growth in bone has increased in recent years, and in this review we shall describe current knowledge of these mechanisms and of the predilection of certain types of cancers to metastasize to bone, their growth in the bone microenvironment and interactions between them and bone cells. Because metastatic breast cancer has been studied more than any other, we shall focus on it as a representative example, although the general principles apply to other types of cancer and to myeloma.
 ...
PMID:Factors regulating the growth of metastatic cancer in bone. 1051 50

Malignant osteolysis is a common complication of many cancers, most notably breast cancer, prostate cancer, and multiple myeloma. Hypercalcemia, pain, and fractures are the main manifestations. Malignant osteolysis can be fatal or cause a rapid deterioration in quality of life. The underlying mechanism in tumor cem-mediated activation of osteoclasts, whose function is normally to resorb bone. It follows that pharmacological agents capable of inhibiting osteoclast activity, including bisphosphonates, are likely to be useful in the treatment of malignant osteolysis. Also, experimental evidence suggest that bisphosphonates act on the tumor cells themselves, either by inhibiting mechanisms involved in the development of bone metastasis (tumor invasion, adhesion of tumor cells to the bone matrix) or by inducing apoptosis of tumor cells. Many clinical trials have found bisphophonates to be effective in the treatment of complications due to malignant osteolysis. Based on these studies, bisphosphonates are now indicated to treat hypercalcemia and to prevent skeletal complications of metastatic breast cancer and myeloma, in a dosage of 1600 mg.d orally for clodronate or 90 mg every four weeks intravenously for pamidronate. Osteoclast inhibition is clearly the mechanism underlying the efficacy of bisphosphonates in these clinical trials. Recent clinical trials found that prophylactic bisphosphonates therapy in patients with nonmetastasic breast cancer decreased the incidence of bone metastases, thus supporting a direct effect of biphosphonates on tumor cells. However, conflicting experimental and clinical data have been reported, so that it remains uncertain whether bisphosphonates have anti-tumor effects in vivo in humans. Nevertheless, biphosphonates now have an undisputed place in the therapeutic armamentarium for cancer.
 ...
PMID:Mechanisms of action of bisphosphonates on tumor cells and prospects for use in the treatment of malignant osteolysis. 1077 65

Bisphosphonates have been used successfully for many years in the treatment of hypercalcaemia and to reduce skeletal complications of metastases. In the first years of bisphosphonate use the efficacy of these substances was thought to lie purely in the inhibition of osteoclasts. However, there is recent evidence to suggest that an antitumour effect may also play a role. As well as having an apoptotic and antiproliferative effect on osteoclasts, bisphosphonates may exert a similar influence on macrophages and tumour cells. Whether this effect (at low doses) also plays a role in vivo remains unclear and requires further investigation. Improvements in the survival time of certain subpopulations have been found in many phase III studies with bisphosphonates to date, both in the setting of metastatic breast cancer and in multiple myeloma. However, because survival time in subgroups of patients was neither a primary nor a secondary objective in these studies, these advantages could only be seen as important pointers for future studies. Some preclinical studies have shown that down-regulation of bone metabolism by bisphosphonates is associated with a lower incidence of bone metastases and destruction in animals, whereas activation is correlated with a higher number of metastases. However, varying results were found in animal experiments with regard to the effect of bisphosphonates on the incidence and growth pattern of non-osseous metastases. The results of 3 randomised studies in patients with primary breast cancer who received clodronate 1600 mg/day orally have now been evaluated and presented. All 3 studies arrived at different results. In the Heidelberg study there was a reduction in both osseous and non-osseous metastases, whereas in a much larger study performed in Great Britain, Canada and Scandinavia there was a reduction only in the incidence of skeletal metastases. A third study from Finland found no effect on bone metastases, but an increase in the number of visceral metastases and a deterioration in overall survival. Because the dosage was identical in all 3 studies, the differing results can only be either random or methodological (for example inclusion criteria or sample size). Overall, the results are very promising, but there is a need for further studies.
 ...
PMID:Antitumour effects of bisphosphonates: first evidence and possible mechanisms. 1077 26

Bendamustine is a bifunctional alkylating agent with cytotoxic activity against human ovarian and breast cancers in vitro. It shows only partial in vitro cross-resistance with cyclophosphamide, melphalan, carmustine and cisplatin. Bendamustine as monotherapy or as part of combination chemotherapy protocols for first-line or subsequent treatment produced objective response rates of 61 to 97% in patients with Hodgkin's disease or non-Hodgkin's lymphoma (NHL) [41 to 48% in high grade NHL]. In patients with multiple myeloma, a bendamustine/prednisone regimen produced a higher rate of complete response (32 vs 11%) and more durable responses than a melphalan/prednisone regimen. Substitution of bendamustine for cyclophosphamide in a standard first-line COP regimen (cyclophosphamide, vincristine and prednisolone) yielded similar response rates in patients with advanced low grade NHL. Substituting bendamustine for cyclophosphamide in the CMF protocol (cyclophosphamide, methotrexate and fluorouracil) prolonged remission from 6.2 to 15.2 months in patients with metastatic breast cancer. The most common adverse events in patients receiving bendamustine are haematological events and gastrointestinal disturbances. Bendamustine has a relatively low propensity to induce alopecia.
 ...
PMID:Bendamustine. 1136 87

Early absolute lymphocyte count (ALC) recovery at day 15 post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival in multiple myeloma and non-Hodgkin's lymphoma. The relationship of ALC with clinical outcomes in metastatic breast cancer is unknown. We evaluated all 29 patients with metastatic breast cancer who underwent ASCT at the Mayo Clinic, Rochester, Minnesota, from 1994 to 1999. The ALC threshold was set at 500 cells/microl on day 15 post-ASCT based on previous experience with hematologic malignancies. All patients were followed for a minimum of 2 years or until death, with a median follow-up for living patients of 2.25 years. Of the 29 patients, 17 have died with disease progression, two are alive and have progressed, and 10 are alive without progression. The median overall and progression-free survival times were significantly better for the 20 patients with ALC > or = 500 cells/microl compared with the nine patients with ALC <500 cells/microl (not reached vs 14 months, P < 0.0001; 24 vs 7 months, P < 0.0015, respectively). In conclusion, ALC > or = 500 cells/microl on day 15 post-ASCT was associated with significantly better survival in patients with metastatic breast cancer, suggesting the importance of early immune recovery post-ASCT in these patients.
 ...
PMID:Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer. 1262 98

Pamidronate is used frequently to treat malignancy-associated hypercalcemia and osteolytic lesions. This widely used bisphosphonate has been noted to cause nephrotoxicity in patients with multiple myeloma and metastatic breast cancer. We encountered a patient with Langerhans's histiocytosis who developed nephrotic syndrome and renal failure after pamidronate therapy. We describe the clinical and renal biopsy findings in this patient.
 ...
PMID:Pamidronate-associated nephrotoxicity in a patient with Langerhans's histiocytosis. 1208 88

Absolute lymphocyte count (ALC) recovery correlates with survival after autologous hematopoietic stem cell transplantation (AHSCT) for patients with multiple myeloma, non-Hodgkin's lymphoma, and metastatic breast cancer. The role of ALC recovery in relationship to clinical outcome after AHSCT in patients with acute myelogenous leukemia is unknown. We analyzed 45 patients who underwent AHSCT at Mayo Clinic, Rochester, Minnesota between 1990 and 2000. The ALC threshold was selected at 500 cells/microl on day 15 post-AHSCT based on our previous studies. Thirty-two females and 13 males were included in the study with a median age of 45 years (range 12-75). The median follow-up was 14 months with a maximum of 129 months. The median overall and leukemia-free survival were significantly better for the 23 patients with ALC at day 15 > or =500 cells/microl compared with 22 patients with ALC <500 cells/microl (not yet reached vs 10 months, P < 0.0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC > or =500 cells/microl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies.
 ...
PMID:Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia. 1209 55


<< Previous 1 2 3 4 5 6 Next >>