Oncology/Hematology

A clinical trial looked at the efficacy of gabapentin compared with venlafaxine, utilizing patient preference as its primary endpoint.  Patients were randomly assigned to receive venlafaxine compared with gabapentin in relatively standard doses recommended by previous placebo-controlled clinical hot flash trials.  Patients were treated for 4 weeks and then had a 2-week washout period, before being crossed-over to the alternative treatment.  Although both agents appeared to reduce hot flashes to similar extents (approximately a 65% (reduction) and had similar amounts of toxicities, 68% of patients preferred venlafaxine compared with 32% who preferred gabapentin (p = 0.01).  The authors concluded that venlafaxine should be recommended as an initial treatment but that some patients did better with gabapentin, supporting a trial of this medication if venlafaxine was not efficacious enough.  In 2013, paroxetine was FDA-approved for the treatment of hot flas...

Paclitaxel produces a disabling syndrome of subacute aches and pains in a majority of patients, which had been commonly referred to as arthralgias and myalgias.  These symptoms generally begin 1 to 3 days after administration and are self-limited, usually resolving within a week.  Symptoms have been described in large axial muscular and joint regions and generally are not accompanied by objective musculoskeletal or neurologic examination changes. The symptom location, temporal relationship, and self-limited nature of the syndrome make paclitaxel-induced acute pain syndrome (APS) distinct from paclitaxel-associated peripheral neuropathy.  In the more distant past, the exact characterization of paclitaxel-induced APS had not been well defined. There had been very little known about how exactly patients characterize these symptoms or how these symptoms compare or contrast to symptoms of neuropathy. Given that paclitaxel, administered to rats, causes dorsal root ganglion ...

Surgical resection followed by involved-field RT plus concurrent temozolomide followed by up to six cycles of adjuvant temozolomide.  Adjuvant temozolomide alone may be considered in elderly patients with poor performance status, especially for O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylated tumors.  Adjuvant radiation therapy alone may be considered in elderly patients with MGMT promoter UNmethylated tumors Bevacizumab is FDA approved for the treatment of recurrent glioblastoma. It's addition in the adjuvant setting didn't improve survival.

-  RET germline mutation is found in Multiple Endocrine Neoplasia Type II. - TP53 mutation is found in Li-Fraumeni syndrome. -  MLH1 mutation is found in Lynch syndrome.

Mantle cell lymphoma may be difficult to differentiate clinically at the time of presentation from chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone lymphoma, or lymphoplasmacytic lymphoma.  Mantle cell lymphoma is best diagnosed by either demonstration of cyclin D1 overexpression by immunohistochemistry or presence of the t(11;14) translocation by FISH. This translocation juxtaposes the immunoglobulin heavy chain region on chromosome 14 with the cyclin D1 gene (BCL1) on chromosome 11.  Flow cytometry is also very helpful if the typical mantle cell lymphoma immunophenotype is expressed, namely, strong expression of monoclonal immunoglobulin on the cell surface as well as strong expression of CD5, CD19, CD20, and CD22, with absence of expression of CD10 and CD23.  The immunophenotype typical of chronic lymphocytic leukemia, will have low levels of surface immunoglobulin and CD20 expression in association with expression of both CD5 and CD23. ...

Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-B (RANK) ligand, preventing activation of RANK, which disrupts osteoclast maturation and activation. The most common adverse event overall was hypocalcemia, which occurred in 5% of patients despite supplementation with vitamin D and calcium.  The most common severe adverse event was hypophosphatemia, which occurred in 3% of patients. Osteonecrosis of the jaw is an infrequent but serious complication of treatment with denosumab. 

Imatinib (400 mg daily) is the standard first-line drug therapy for treatment of locally advanced or metastatic GIST.  Approximately 35% of patients with metastatic GIST harboring mutation in exon 9 of KIT demonstrated objective response to treatment with imatinib in one large trial.  Retrospective analyses of patients with KIT exon 9–mutant GIST crossing over to the higher dose of 400 mg twice daily of imatinib demonstrated significant benefit in approximately 50% of the patients, and dose escalation is a reasonable first step in a patient who has no significant adverse effects on the lower dose.  In a phase I trial of imatinib in patients with sarcoma, dose-limiting toxicities were encountered at daily doses of 1,000 mg. An antitumor advantage of 1,200 mg per day versus 800 mg per day has not been established.  Surgical debulking has not obtained long-term control of GIST in patients with multifocal tumor progression.  Sunitinib is the only drug approv...

Ipilimumab is associated with significant toxicities that are immune-related adverse events.  These immune-mediated reactions may involve any organ system; however, the most common immune-adverse reactions are enterocolitis, hepatitis, dermatitis, neuropathy, and endocrinopathy.  Treatment of immune-mediated toxicity requires interruption of ipilimumab and use of corticosteroids depending upon severity of symptoms. The FDA has created a Risk Evaluation and Mitigation Strategy to provide additional information regarding side effects and management of ipilimumab-associated adverse events.  Therefore, it is recommended that patients undergoing treatment with ipilimumab be monitored closely with physical exams, review of symptoms, and blood tests including liver and thyroid function before and during treatment.  Dose modification occurs through withholding a dose, not dose reduction.

Esophageal cancer is a disease with an extraordinarily high risk of recurrence after surgical resection. Preoperative chemoradiation followed by surgery was established as the standard of care for locally advanced esophageal cancer (T3 tumors or positive lymph nodes) in the CROSS trial investigating radiation (41.4 Gy) given with weekly carboplatin (AUC=2) and paclitaxel (50 mg/m2) followed by surgery compared to surgery alone. Five year survival rates were increased from 34% with surgery alone to 47% with trimodality therapy. Esophagectomy alone is appropriate for early stage disease (T12, N0). Definitive chemoradiation has an excellent cure rate in early stage squamous cell carcinomas, but adenocarcinomas are unlikely to be cured with chemoradiation alone. It is important to recognize the benefit of trimodality therapy in locally advanced adenocarcinoma of the esophagus. If this tumor were a squamous cell carc...