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Telotristat for Refractory Carcinoid Syndrome Diarrhea
Telotristat inhibits the production of serotonin by carcinoid tumors and reduces the frequency of carcinoid syndrome diarrhea. The randomized TELESTAR trial compared two doses of oral telotristat (250 mg and 500 mg, each taken three times daily) against placebo in 135 patients who had uncontrolled symptoms from carcinoid syndrome despite treatment with a somatostatin analog. Treatment with telotristat at either dose was associated with a reduction in bowel movement frequency compared with placebo, and the drug was well tolerated. Based upon these results, telotristat has been approved in the United States, in combination with somatostatin analog therapy, for the treatment of adults with diarrhea related to carcinoid syndrome that is inadequately controlled by somatostatin analog therapy alone. The recommended dose is 250 mg three times daily.
Immunotherapy for Metastatic Urothelial Carcinoma
Cisplatin-based chemotherapy is the preferred initial treatment for patients with metastatic urothelial carcinoma of the bladder and upper urinary tract; however, most patients eventually relapse. In a phase III trial in patients who had recurred after or progressed on a platinum-containing regimen, pembrolizumab prolonged overall survival compared with second-line chemotherapy (paclitaxel, docetaxel, or vinflunine). For patients who relapse following treatment with a platinum-based regimen, we recommend checkpoint inhibition with an agent targeting the programmed cell death-1 (PD-1) protein or its ligand (PD-L1).
Early Initiation of Palliative Care and Survival
When initiated early in the disease course, palliative care improves clinical and quality of care outcomes; randomized trials in patients with cancer or advanced lung disease also report a survival advantage, although more diverse palliative care populations have not been studied. A meta-analysis of seven randomized trials involving 2184 patients concluded that there was no association between early initiation of palliative care and overall survival. Previous reports of a possible survival advantage may have reflected bias in patient selection; only one of the seven trials was rated as having a low risk of bias.
Scalp Hypothermia to Prevent Chemotherapy-Induced Alopecia
Two prospective studies have evaluated the efficacy of two different automated scalp cooling devices in women with early stage breast cancer:
* In an interim analysis of a randomized trial comparing the Paxman Scalp Cooling device and no scalp hypothermia for women with breast cancer receiving adjuvant chemotherapy (one-third anthracycline-based, the remainder taxane-based), one-half of the hypothermia group had limited hair loss (to less than 50 percent, not requiring a wig) compared with none in the control group. Adverse events were all grade 1 and 2, including primarily headache and feeling cold. The success rate was higher with taxane-containing regimens.
* In a multicenter prospective cohort study, 101 patients receiving non-anthracycline taxane-based chemotherapy and who used the DigniCap Scalp Cooling device were compared with 16 concurrently treated controls who did not use the device. Two-thirds of the intervention group, compared with none of the control group, had limited hair loss (to less than 50 percent) one month after the end of chemotherapy. At a median follow-up of 2.5 years, no patient developed scalp metastases.
These results confirm prior studies on the efficacy and safety of scalp hypothermia to reduce chemotherapy-induced alopecia. One of these devices (DigniCap) is FDA-cleared for this use in the United States.
Targeted Therapy for Advanced Melanoma With an NRAS Mutation
Binimetinib, an inhibitor of MEK, is able to block the MAPK pathway in patients with advanced melanoma and an NRAS driver mutation. In a phase III trial in this patient population, binimetinib significantly prolonged progression-free survival compared with chemotherapy in patients who had progressed during or after immunotherapy. Binimetinib is not currently approved for use outside of a clinical trial setting.