Thanarajasingam, Gita

Malignant cells may subvert and escape endogenous host immune surveillance by up‐regulation of immune inhibitory signals known as immune checkpoints. These checkpoints are important therapeutic targets, and antibodies that block checkpoint signaling have shown remarkable efficacy in some solid tumors as well as in some refractory hematologic malignancies. In hematologic cancers, the mechanism of these checkpoints is complex, as the tumor and immune system are one and the same. In this review, we evaluate the biology of checkpoint inhibition, review the current data on its efficacy in lymphoid tumors, and explore uncertainties in the field, including those involving the precise mechanisms of action, the appropriate timing of therapy, and the differences in response rate between lymphoid tumor types.

The liver is the dominant site of metastases for patients with metastatic colorectal cancer (mCRC). Depending on the timing of diagnosis and the biology of the disease, it is not uncommon for these patients to present with visceral crisis in the form of severe liver dysfunction. Treatment of these individuals is, however, difficult and challenging. The decision to consider chemotherapy in these dire circumstances entails consideration of numerous factors. If we were to focus on just the metabolism of the different drugs and biologic agents available to treat mCRC, both 5-fluorouracil and oxaliplatin alone or in combination with a monoclonal antibody are reasonable choices. Specifically, FOLFOX is a feasible and safe option in patients with mCRC with severe liver dysfunction. Choice of the biologic agent to add to the doublet chemotherapy could be individualized based on the RAS status and the clinical scenario. Based on the divergent experience of treating 2 cases and other prior reports, a summary of recommendations with a model in the form of a “therapeutic triad” is presented. The paper highlights the therapeutic challenges in patients with mCRC and severe liver dysfunction. The choice of chemotherapeutic agents and reports of other cases/series is also presented.

A 73-year-old woman with a history of localised transitional cell cancer (TCC) of the bladder, resected 22 years prior, presented with tremor, gait unsteadiness and cognitive deficits. Basic neurological workup was negative and CT of the abdomen revealed recurrent TCC with a solitary pelvic metastasis. She was treated with surgical resection of her tumour and immunosuppression. Her symptoms resolved, and it was felt her presentation was consistent with paraneoplastic encephalopathy in the setting of bladder cancer metastasis. She has remained disease and symptom free over 5 years of follow-up. This case report reviews the mechanism, clinical features and treatment of paraneoplastic neurological syndromes, and discusses briefly the management of oligometastatic recurrent bladder cancer.

BACKGROUNDDespite targeted antiemetics, data support an unmet need related to the management of delayed nausea and vomiting (NV). Promising pilot data informed this phase III trial evaluating gabapentin for delayed NV from highly emetogenic chemotherapy (HEC).METHODSParticipants were randomized to receive prophylactic treatment with 20 mg of dexamethasone and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by gabapentin 300 mg twice a day and dexamethasone (dex) or placebo and dex after HEC. Gabapentin/placebo was started the day of chemotherapy and continued through day 5 for the first chemotherapy cycle, whereas dex was titrated down on days 2‐4. The primary end point was complete response (CR), defined as no emesis and no use of rescue medications on days 2‐6, using an NV diary. The percentages of those in each group with a CR were compared by Fisher's exact test.RESULTSFour hundred thirty patients were enrolled in this study. Forty‐seven percent of patients in the gabapentin arm and 41% in the placebo arm had a CR (P = .23). Mean number of emesis episodes was <0.5 daily, and mean nausea severity was < 2 (mild). In both arms, patient satisfaction with NV control was greater than 8 (with 10 being perfectly satisfied). There were no significant differences in unwanted side effects.CONCLUSIONSIn this study, gabapentin did not significantly improve delayed NV. Patients were satisfied with the control of their nausea and vomiting irrespective of arm. The use of a 5HT3 RA and dexamethasone provided good control of nausea and vomiting for most patients. Cancer 2014;120:3575–3583. © 2014 American Cancer Society.