To evaluate the effect of high-dose chemotherapy in the treatment of metastatic breast cancer, we performed a phase II trial of a single treatment with high-dose cyclophosphamide (5,625 mg/m2), cisplatin (165 mg/m2), and carmustine (600 mg/m2), or melphalan (40 mg/m2) and bone marrow support as the initial chemotherapy for metastatic breast cancer. Twenty-two premenopausal patients with estrogen receptor negative, measurable metastatic disease were treated. Twelve of 22 patients (54%) obtained a complete response at a median 18 days. The overall response rate is 73% (complete and partial response). Median duration of response in the patients achieving complete response was 9.0 months with a median duration of survival for complete responders that is currently undefined. Relapse occurred predominantly at sites of pretreatment bulk disease or within areas of previous radiation therapy. Toxicity was frequent and five patients died of therapy-related complications. The results indicate that a single treatment with intensive combination alkylating agents with bone marrow support can produce more rapid and frequent complete responses than conventional chemotherapy when used as initial chemotherapy for metastatic breast cancer, although median disease-free and overall survival is not improved. Three patients (14%) remain in unmaintained remission beyond 16 months.

• Frontline brentuximab vedotin monotherapy provided a 92% ORR and was generally well tolerated in elderly HL patients.Outcomes in older patients with Hodgkin lymphoma (HL) tend to be poor following conventional chemotherapy regimens. Treatment-related toxicity is significant and comorbidities often limit therapeutic options. This phase 2, open-label study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, as frontline therapy in 27 HL patients aged ‡60 years. The objective response rate (ORR) was 92%, with 73% achieving complete remission. All patients achieved stable disease or better, and had decreased tumor volume following treatment. At the time of this analysis, the median duration of objective response for efficacy-evaluable patients (N 5 26) was 9.1 months (range, 2.8 to 20.91 months), median progression-free survival was 10.5 months (range, 2.61 to 22.31 months), and median overall survival had not been reached (range, 4.61 to 24.91 months). The observed adverse events (AEs) were generally consistent with the known safety profile of brentuximab vedotin. The most common AEs were peripheral sensory neuropathy (78%), fatigue (44%), and nausea (44%), and were £ grade 2 for most patients. The incidence of grade 3 peripheral neuropathy events was relatively high (30% overall), particularly among patients with the known risk factors of diabetes and/or hypothyroidism (46% vs 14% for those without). However, these risk factors were not associated with delayed time to resolution/improvement of peripheral neuropathy. Preliminary data showed no substantial age-related changes in brentuximab vedotin pharmacokinetics. Brentuximab vedotin monotherapy may provide a frontline treatment option for older patients who cannot tolerate conventional combination chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806. (Blood. 2015;126(26):2798-2804

Patients aged ≥60 years with treatment-naive Hodgkin lymphoma (HL) have few treatment options and inferior survival due to treatment-related toxicities and comorbidities. This phase 2, nonrandomized, open-label study evaluated brentuximab vedotin (BV) monotherapy (results previously reported), BV plus dacarbazine (DTIC), and BV plus bendamustine. Patients had classical HL and were ineligible for or declined frontline chemotherapy. Twenty-two patients received 1.8 mg/kg BV and 375 mg/m DTIC for up to 12 cycles, and 20 more patients received 1.8 mg/kg BV plus 90 or 70 mg/m bendamustine for up to 6 cycles (dose reduced due to toxicity). Subsequent BV monotherapy was allowed. Approximately 30 patients were to receive BV plus bendamustine; however, the incidence of serious adverse events (65%) and 2 deaths on study led to discontinuation of bendamustine and cessation of enrollment. Most patients had stage III/IV disease, and approximately half had ≥3 comorbidities or were impaired in ≥1 aspect that significantly interfered with quality of life. For BV plus DTIC, the objective response rate (ORR) was 100% and the complete remission (CR) rate was 62%. To date, the median progression-free survival (PFS) is 17.9 months. For BV plus bendamustine, the ORR was 100% and the CR rate was 88%. Neither the median PFS nor overall survival was reached. For elderly patients with HL, BV plus DTIC may be a frontline option based on tolerability and response duration. Despite activity, BV plus bendamustine is not a tolerable regimen in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01716806.

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The effect of treatment with exogenous interferon was compared with those of two interferon inducers, polyriboinosinic-polyribocytidylic acid [poly(I) . poly(C)] and poly(I) . poly(C)-poly-L-lysine complex [poly(ICLC)], in three model Herpesvirus hominis type 2 infections of mice. After intraperitoneal inoculation of H. hominis type 2, all drugs significantly protected animals against death and increased the mean day of death when administered as late as 48 hr after viral inoculation. With intranasal inoculation of H. hominis type 2, pretreatment with poly (I) . poly (C) and poly (ICLC) increased the mean day of death; however, no drug prevented death. In mice inoculated intravaginally, local treatment with exogenous interferon or poly(I) . poly(C) appeared to reduce the mean titers of virus in genital secretions and resulted in earlier clearance of infection in some animals. Systemic treatment of genital H. hominis type 2 infections with all drugs resulted in significant numbers of infected animals surviving the infection, although the mean titers of virus in genital secretions were unchanged. Therapeutic efficacy varied depending on the route of viral inoculation.