Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer.

BACKGROUND: Nelfinavir (NFV), an HIV-1 protease inhibitor, has been shown to sensitize cancer cells to chemoradiation (CRT). The objectives of this phase 1 trial were to evaluate safety and identify the recommended phase 2 dose of NFV added to concurrent CRT for locally advanced cervical cancer. METHODS: Two dose levels of NFV were evaluated: 875 mg orally twice daily (dose level 1 [DL1]) and 1250 mg twice daily (DL2). NFV was initiated 7 days before CRT and continued through CRT completion. Toxicity, radiographic responses, and pathologic responses were evaluated. Serial tumor biopsies (baseline, after NFV monotherapy, on NFV + CRT, and posttreatment) were evaluated by immunohistochemistry, NanoString, and reverse-phase-protein-array analyses. RESULTS: NFV sensitized cervical cancer cells to radiation, increasing apoptosis and tumor suppression in vivo. Patients (n = 13) with International Federation of Gynecology and Obstetrics stage IIA through IVA squamous cell cervical carcinoma were enrolled, including 7 patients at DL1 and 6 patients at DL2. At DL1, expansion to 6 patients was required after a patient developed a dose-limiting toxicity, whereas no dose-limiting toxicities occurred at DL2. Therefore, DL2 was established as the recommended phase 2 dose. All patients at DL2 completed CRT, and 1 of 6 experienced grade 3 or 4 anemia, nausea, and diarrhea. One recurrence was noted at DL2, with disease outside the radiation field. Ten of 11 evaluable patients remained without evidence of disease at a median follow-up of 50 months. NFV significantly decreased phosphorylated Akt levels in tumors. Cell cycle and cancer pathways also were reduced by NFV and CRT. CONCLUSIONS: NFV with CRT is well tolerated. The response rate is promising compared with historic controls in this patient population and warrants further investigation.

Promoting knowledge of cancer prevention and screening in an underserved Hispanic women population: a culturally sensitive education program.

This article aims to measure the baseline knowledge of cancer prevention, screening, and early detection practices, to understand the barriers to cancer screening and sources of health information; and to evaluate the effectiveness of a culturally sensitive education program in an underserved Hispanic women population. A total of 180 women participated. Pre- and postsurveys were administered. Multivariate analysis was used to analyze the impact of program on knowledge and to determine factors affecting learning. Results showed Significant overall improvement in knowledge of cancer symptoms (1.85 baseline vs. 3.67 postintervention, p < .001), knowledge of risk-reducing behaviors (2.71 vs. 4.81, p < .001); and effect on planned behavior (89% planned to follow screening guidelines). Higher incomes and younger age are associated with better learning. Major barriers to cancer screening were financial limitations and lack of knowledge. The intervention was effective in promoting awareness and knowledge of cancer screening and prevention. Programs aimed at reducing cancer incidence and mortality should recognize the importance of cultural sensitivity and facilitating access to screening tests.