Purpose This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. Patients and Methods Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility. Results From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy sign...

Randomized Phase III Trial of Capecitabine Compared With Bevacizumab Plus Capecitabine in Patients With Previously Treated Metastatic Breast Cancer

Purpose: To update the 2000 ASCO guidelines on the role of bisphosphonates in women with breast cancer and address the subject of bone health in these women. Results: For patients with plain radiographic evidence of bone destruction, intravenous pamidronate 90 mg delivered over 2 hours or zoledronic acid 4 mg over 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence supporting the efficacy of one bisphosphonate over the other. Starting bisphosphonates in women who demonstrate bone destruction through imaging but who have normal plain radiographs is considered reasonable treatment. Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bone destruction is not recommended. The presence or absence of bone pain should not be a factor in initiating bisphosphonates. In patients with a serum creatinine less than 3.0 mg/dL (265 μmol/L), no change in dosage, infusion time, or interval is required. Infusion times less than 2 hours with pamidronate or less t...

American Society of Clinical Oncology 2003 Update on the Role of Bisphosphonates and Bone Health Issues in Women With Breast Cancer

Focal segmental glomerulosclerosis, which is characterized by progressive glomerular scarring, accounts for about 20% of cases of the nephrotic syndrome in children and 40% in adults. This review considers current approaches to diagnosis and management of the disease.

/pdf/focal-segmental-glomerulosclerosis-18olz8vich.pdf

Focal segmental glomerulosclerosis.

Pathologic classification of focal segmental glomerulosclerosis: a working proposal.

Neurotoxic side effects of cancer therapy are second in frequency to hematological toxicity. Unlike hematological side effects that can be treated with hematopoietic growth factors, neuropathies cannot be treated and protective treatment strategies have not been effective. For the neurologist, the diagnosis of a toxic neuropathy is primarily based on the case history, the clinical and electrophysiological findings, and knowledge of the pattern of neuropathy associated with specific agents. In most cases, toxic neuropathies are length-dependent, sensory, or sensorimotor neuropathies often associated with pain. The platinum compounds are unique in producing a sensory ganglionopathy. Neurotoxicity is usually dependent on cumulative dose. Severity of neuropathy increases with duration of treatment and progression stops once drug treatment is completed. The platinum compounds are an exception where sensory loss may progress for several months after cessation of treatment ("coasting"). As more effective multiple drug combinations are used, patients will be treated with several neurotoxic drugs. Synergistic neurotoxicity has not been extensively investigated. Pre-existent neuropathy may influence the development of a toxic neuropathy. Underlying inherited or inflammatory neuropathies may predispose patients to developing very severe toxic neuropathies. Other factors such as focal radiotherapy or intrathecal administration may enhance neurotoxicity. The neurologist managing the cancer patient who develops neuropathy must answer a series of important questions as follows: (1) Are the symptoms due to peripheral neuropathy? (2) Is the neuropathy due to the underlying disease or the treatment? (3) Should treatment be modified or stopped because of the neuropathy? (4) What is the best supportive care in terms of pain management or physical therapy for each patient? Prevention of toxic neuropathies is most important. In patients with neuropathy, restorative approaches have not been well established. Symptomatic and other management are necessary to maintain and improve quality of life.

Chemotherapy-induced neuropathy.

Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.

Collapsing Focal Segmental Glomerulosclerosis Following Treatment with High-Dose Pamidronate

It is now recognized that all cases of multiple myeloma (MM) are preceded by the premalignant condition of monoclonal gammopathy of undetermined significance (MGUS). Although patients with MGUS are generally asymptomatic and currently managed by "watch and wait," the identification of high-risk patients whose disease will progress more rapidly to smoldering MM (SMM) and MM aids in timely intervention. The immunomodulatory agents thalidomide and lenalidomide and the proteasome inhibitor bortezomib are now routine components of MM therapy in both first-line and relapsed/ refractory settings. These targeted agents are used in various combinations with chemotherapy for the treatment of both transplantation-ineligible and transplantation-eligible patients. More recently, a trend toward evaluation of 3- and 4-drug multiagent combinations before transplantation and prolongation of primary therapy has generated new treatment paradigms. Ultimately, the physician's choice of therapy and treatment strategy requires consideration of regimen-associated toxicities and integration of the patient's risk, comorbid status, and response and tolerability of previous treatment regimens. Particular attention needs to be paid to baseline and/or treatment-emergent peripheral neuropathy, thrombotic risk, changes in renal function, and bone health. Despite recent advances, all patients with MM eventually relapse, and efforts to identify novel synergistic combinations and new agents are ongoing. This review highlights challenges in the clinic and newer approaches under evaluation for the treatment and/or management of patients with MGUS, SMM, and MM.

https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)70082-9/pdf

The Current Status and Future of Multiple Myeloma in the Clinic

Multiple myeloma is an incurable clonal B-cell malignancy with terminally differentiated plasma cells that accounts for 1% of all malignancies in the United States. It may present with tumors consisting of discrete masses of neoplastic monoclonal plasma cells in either bone or soft tissues. Central nervous system (CNS) involvement of myeloma is uncommon and is observed in approximately 1% of cases. It may manifest as dural myeloma or intraparenchymal infiltration, or with diffuse leptomeningeal involvement. Dural involvement of myeloma without parenchymal or leptomeningeal disease is an even rarer occurrence, with only 5 cases reported in the medical literature. There are no established treatment guidelines for CNS myelomatosis; prognosis and literature on the use of treatment modalities for this complication is reviewed herein.

https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)70010-6/pdf

Sundar Jagannath

Papers

Collapsing Focal Segmental Glomerulosclerosis Following Treatment with High-Dose Pamidronate

The Current Status and Future of Multiple Myeloma in the Clinic

Intracranial Multifocal Dural Involvement in Multiple Myeloma: Case Report and Review of the Literature

Thalidomide and lenalidomide in multiple myeloma

Plasmacytoma in the breast with axillary lymph node involvement: a case report.