For patients with previously untreated mantle-cell lymphoma who are either ineligible for or are not candidates for intensive chemotherapy and stem-cell transplantation, the standard of care is the combination regimen of rituximab (Rituxan), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisolone (R-CHOP). Studies showed that this could produce complete responses in up to 48% of patients, but progression-free survival (PFS) is limited. The proteasome inhibitor bortezomib (Velcade) was initially approved by the FDA for the treatment of relapsed mantle-cell lymphoma. Now, in a phase 3 trial, researchers assessed the efficacy and safety of bortezomib as frontline therapy in a regimen of bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus R-CHOP in patients with newly diagnosed disease (Robak T, et al. N Engl J Med. 2015;372:944-953).
For the study, 487 patients with newly diagnosed mantle-cell lymphoma who were ineligible for or who are not candidates for stem-cell transplantation were randomized to 1 of 2 combination regimens. Patients could receive six to eight 21-day cycles of R-CHOP (N = 244) intravenously on day 1 (with prednisone administered orally on days 1-5) or VR-CAP (N = 243; R-CHOP regimen, but substituting vincristine with bortezomib at a dose of 1.3 mg/m2 of body surface area on days 1, 4, 8, and 11). The primary end point was PFS. The secondary end points included complete response rate, duration of complete response, time to progression, time to next antilymphoma therapy, treatment-free interval, overall survival, and safety.
After a median follow-up of 40 months, 61% of patients had disease progression or died. The median PFS was 14.4 months in the R-CHOP group compared with 24.7 months in the VR-CAP group (hazard ratio [HR], 0.63; P <.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of PFS were 16.1 months and 30.7 months, respectively (HR, 0.51; P <.001). The secondary end points were consistently improved in the VR-CAP group versus the R-CHOP group, including the complete response rates (42% vs 53%, respectively), median duration of complete response (18.0 vs 42.1 months, respectively), median time to progression (16.1 vs 30.5 months, respectively), median time to next antilymphoma therapy (24.8 vs 44.5 months, respectively), and the median treatment-free interval (20.5 vs 40.6 months, respectively). The researchers noted that overall survival was not mature at the time of the report; however, there was a difference in 4-year survival between the VR-CAP and R-CHOP cohorts (54% vs 64%, respectively).
Adverse events (AEs) of any grade and discontinuation as a result of AEs were similar in both treatment groups, but patients in the VR-CAP group had higher rates of serious AEs. Hematologic toxic effects were the most common AEs, with grade ?3 AEs for neutropenia and thrombocytopenia higher in the VR-CAP group (85% and 57%, respectively).
Overall, VR-CAP prolonged the duration of PFS and showed improvements in secondary end points compared with R-CHOP in patients with newly diagnosed mantle-cell lymphoma. This improvement was accompanied by increased hematologic toxicity.
Early ovarian failure is a common long-term side effect of chemotherapy. Patients with cancer and premature ovarian failure are at an increased risk for menopausal symptoms, osteoporosis, and infertility. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. In a new study, researchers evaluated whether administration of the GnRH agonist goserelin (Zoladex) with chemotherapy would reduce the rate of ovarian failure after adjuvant or neoadjuvant treatment of hormone receptor–negative early breast cancer (Moore HC, et al. N Engl J Med. 2015;372:923-932).
The Prevention of Early Menopause Study (POEMS) is an international, randomized, phase 3 study that included 218 premenopausal women aged 18 to 49 years with stage I to IIIA operable hormone receptor–negative breast cancer. Patients were randomized in a 1:1 ratio to goserelin with chemotherapy (N = 105) or chemotherapy alone (N = 113). The dose of goserelin was 3.6 mg administered subcutaneously every 4 weeks beginning 1 week before the initial chemotherapy dose and was continued to within 2 weeks before or after the final chemotherapy dose. An anthracycline-based chemotherapy was used in a total of 91% of patients. Patients with human epidermal growth factor receptor 2–overexpressing tumors were permitted to use trastuzumab (Herceptin). The primary end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone in the postmenopausal range. The secondary end points included pregnancy outcomes, disease-free survival, and overall survival.
After 2 years of treatment, the rate of ovarian failure was 8% in the goserelin group compared with 22% in the chemotherapy-alone group. In addition, at least 1 pregnancy occurred in more women in the goserelin group compared with the chemotherapy-alone group within the first 5 years of posttreatment (21% vs 11%, respectively). The rates of disease-free survival and overall survival were also higher in the goserelin group than in the chemotherapy-alone group (89% and 92% vs 78% and 82%, respectively). Grade 3 AEs occurred in 6 patients in each group. Grade ?2 AEs were observed in 48% of patients in the goserelin group versus in 24% of patients in the chemotherapy-alone group.
Although incomplete enrollment and missing data restricted the interpretation of the findings, the use of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk for early menopause and improving prospects for fertility.
The American Cancer Society and the American Society of Clinical Oncology issued a joint statement outlining recommendations for policymakers as they work to ensure the safety of electronic cigarettes (e-cigarettes) and other electronic nicotine delivery systems (ENDS), and to minimize the potential negative consequences (Brandon TH, et al. J Clin Oncol. 2015;33:952-963).
Some state and local governments have enacted e-cigarette regulations; however, federal regulations have yet to be adopted. Unlike combustible cigarettes and many other tobacco products, the FDA does not currently regulate e-cigarettes and other ENDS. Manufacturing standards and quality controls on e-cigarettes also have yet to be implemented.
Smoking is responsible for 30% of all cancer deaths in the United States and is associated with an increased risk for at least 18 types of cancer. E-cigarettes and ENDS, which are capable of delivering nicotine in an aerosolized form, have been advocated as harm-reduction devices and smoking cessation aids; however, these products can also be harmful if they increase the likelihood of nonsmokers using combustible tobacco products or if they discourage smokers from quitting. Insufficient data exist on the health consequences of using ENDS and on their value as tobacco cessation aids. Therefore, a key recommendation is for additional research on these products, including assessing the health impact of ENDS, understanding the patterns of use for ENDS, and determining what role ENDS have in cessation.
In addition to underscoring the need for more research to inform the regulation of e-cigarettes and ENDS, key policy recommendations include:
