Stella, Philip J.

Purpose A phase II study was conducted to determine the efficacy and toxicity of radiotherapy with concomitant gemcitabine and cisplatin for patients with locally advanced pancreatic adenocarcinoma. Patients and Methods Forty-eight patients with locally advanced pancreatic adenocarcinoma received gemcitabine (30 mg/m2) and cisplatin (10 mg/m2) twice weekly during the first 3 weeks of radiotherapy. The radiation dose to the primary tumor and regional nodes was 45 Gy in 25 fractions, and the gross tumor volume received an additional 5.4 Gy in three fractions. Four weeks after radiotherapy, patients received gemcitabine (1,000 mg/m2) once weekly every 3 of 4 weeks for a 12-week period. The primary end point was survival at 12 months. Secondary end points were time to progression, toxicity, and quality of life. Results Survival at 1 year was 40% for 47 eligible patients. The median survival was 10.2 months. Confirmed responses were observed for 8.5% (two partial, two complete), and median time to progression was 7.3 months. Grade 4 or higher toxicity was observed for 31% and consisted primarily of hematologic and GI toxicity. There was a trend toward improved overall quality of life, measured by the Symptom Distress Scale (P = .06), with significant improvements in domains of insomnia, pain, and outlook. Conclusion The combination of radiotherapy, gemcitabine, and cisplatin was well tolerated. Survival results were similar to those achieved with other treatment regimens for patients with locally advanced pancreatic cancer but did not meet our predefined criteria for additional evaluation of this regimen.

Abstract Purpose: Rituximab is a chimeric antibody that induces B-cell apoptosis and recruits immune effector cells to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic responses by T cells and natural killer cells. This phase II study was done to determine the efficacy and toxicity of IL-12 in combination with rituximab in patients with B-cell non-Hodgkin's lymphoma (NHL). Experimental Design: Fifty-eight patients with histologically confirmed relapsed B-cell NHL were randomized to receive concurrent treatment with rituximab and IL-12 (arm A) or rituximab with subsequent treatment with IL-12 after documented nonresponse or progression after rituximab (arm B). Treatment consisted of 375 mg/m2 rituximab on days 1, 8, 15, and 22 and 300 ng/kg IL-12 given s.c. twice weekly starting on day 2 for arm A or upon progression for arm B. Results: The overall response rate was 37% (11 of 30) in arm A and 52% (13 of 25) in arm B. All of the responses seen in arm B occurred while patients received rituximab, and no responses occurred during treatment with subsequent IL-12. The median duration of response was 16 months for arm A and 12 months for arm B. Biopsy specimens were serially obtained in a subset of patients and showed that changes in gene expression were different when cells from the peripheral blood were compared with cells from lymph node biopsies. Conclusions: The concomitant use of IL-12 and rituximab had modest disease activity in patients with B-cell NHL, but the sequential administration of IL-12 after rituximab did not result in additional clinical responses.

Purpose Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. Methods A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. Results Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. Conclusion This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.

Purpose To answer the question, “should elderly non–small-cell lung cancer patients be offered elderly-specific trials?” Patients and Methods The North Central Cancer Treatment Group (NCCTG) performed a pooled analysis of elderly patients who participated in elderly-specific trials (required age ≥ 65 years) and age-unspecified trials (required age ≥ 18 years). Between 1998 and 2000, all NCCTG non–small-cell lung cancer (NSCLC) patients with incurable cancer, age ≥ 65 years, and receiving first-line chemotherapy were included. A total of 118 elderly patients participated in elderly-specific trials, and 108, in age-unspecified trials. Demographics and outcomes were compared based on trial type. Results The median age of elderly patients in elderly-specific trials was greater: median (range): 73 years (65 to 87) and 70 years (65 to 85), respectively (P < .001), as was the percentage older than 80 years: 17% and 3%, respectively (P = .0008). Median survival times were 232 and 302 days, respectively (P = .08). After adjustment for baseline age, Eastern Cooperative Oncology Group performance score, cancer stage, and body mass index, this survival difference was not statistically significant (hazard ratio = 1.25; P = .16). Grade 3 or worse nonhematologic adverse event rates were greater in age-unspecified trials (81% v 57%, respectively; P < .001), as were grade 3 or worse hematologic events (68% v 10%, respectively; P < .001). Conclusion Elderly patients in NSCLC elderly-specific trials suffered lower rates of severe adverse events with no statistically significant differences in survival. It seems that elderly-specific trials are providing quality care and helping to define optimal cancer therapy in the elderly, particularly among the “oldest of the old.”

Purpose: The North Central Cancer Treatment Group performed a phase III trial to determine whether chemotherapy plus either bid radiation therapy (RT) or daily (qd) RT resulted in a better outcome for patients with stage III non–small-cell lung cancer (NSCLC). No difference in survival was identified between the two arms. This secondary analysis was performed to examine the relationship between patient age and outcome. Patients and Methods: Two hundred forty-six patients were randomized to receive etoposide plus cisplatin and either RT qd or split-course RT bid. This retrospective study compared the outcomes of patients aged ≥70 years (“elderly patients”) with those of younger individuals. Of the 244 assessable patients, 63 (26%) were elderly, and 181 (74%) were younger individuals. Results: The 2-year and 5-year survival rates were 39% and 18%, respectively, in patients younger than 70 years, compared with 36% and 13%, respectively, in elderly patients (P = .4). Grade 4+ toxicity occurred in 62% of patients younger than 70 years compared with 81% of elderly patients (P = .007). Grade 4+ hematologic toxicity occurred in 56% of patients younger than 70 years, compared with 78% of elderly patients (P = .003). Grade 4+ pneumonitis occurred in 1% of those younger than 70 years, compared with 6% of elderly patients (P = .02). Conclusion: Toxicity, especially myelosuppression and pneumonitis, was more pronounced in the elderly patients receiving combined-modality therapy for locally advanced NSCLC. Despite increased toxicity, elderly patients have survival rates equivalent to younger individuals. Therefore, fit, elderly patients with locally advanced NSCLC should be encouraged to receive combined-modality therapy, preferably on clinical trials with cautious, judicious monitoring. Future studies should explore ways to decrease toxicity of therapy in elderly patients.

Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment. Results: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P = .73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P = .12). Conclusion: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.