Treatment of leukemic relapse following unrelated umbilical cord blood transplantation with interleukin-2: potential for augmenting graft-versus-leukemia and graft-versus-host effects with cytokines.

In comparison to bone marrow, umbilical cord blood has decreased intrinsic immune responsiveness allowing transplantation across HLA barriers with lower rates of graft-versus-host disease. However, laboratory models have also suggested that cord blood may be extremely sensitive to stimulation by cytokines. We report an adult recipient of an ex vivo expanded, HLA-mismatched, unrelated cord blood transplant who experienced a late extramedullary relapse while still in hematologic remission. Despite demonstrating immune tolerance on minimal immunosuppressive agents, a brief course of intravenous interleukin-2 resulted in rapid, aggressive graft-versus-host and graft-versus-leukemia reactions. This case highlights the potential of cytokine immunomodulation following cord blood transplantation, but also suggests caution in stimulating these cells.

Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.

BACKGROUND: Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes. OBJECTIVE: To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University of Rochester Cancer Center Community Clinical Oncology Program. PATIENTS: 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy. INTERVENTION: Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks. MEASUREMENTS: In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study. RESULTS: Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups. CONCLUSION: Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.

Use of 5-HT3 receptor antagonists to prevent nausea and emesis caused by chemotherapy for patients with breast carcinoma in community practice settings.

BACKGROUND: Although 5-HT3 receptor antagonists are clinically more effective in controlling emesis, particularly that caused by high dose cisplatin, than previously available agents, they appear to be less effective against nausea. This report focuses on the effectiveness of these agents against nausea and emesis in patients receiving two moderately emetogenic combination chemotherapy regimens as treatment for breast carcinoma in community practice settings. METHODS: Six hundred ninety-two breast carcinoma patients (688 female, 4 male; mean age, 51 years) enrolled in a nonrandomized study completed the Morrow Assessment of Nausea and Emesis (MANE) following 4 consecutive chemotherapy treatments. The frequency, duration, and severity of postchemotherapy nausea (PN) and postchemotherapy emesis (PE) were compared by type of antiemetic (5-HT3 receptor antagonist vs. other) and chemotherapy regimen (cyclophosphamide and doxorubicin with or without 5-fluorouracil [CA/CAF] vs. cyclophosphamide, methrotrexate, and 5-fluorouracil [CMF]). RESULTS: Within each regimen, the mean duration of PN was significantly longer for patients who received a 5-HT3 receptor antagonist than for those who were not given an antiemetic of that type (CA: 40.3 hours vs. 29.6 hours, P < 0.05; CMF: 37.6 hours vs. 30.2 hours, P < 0.05). There were no significant differences in the frequency or severity of nausea or in the frequency, severity, or duration of emesis by type of antiemetic for patients receiving either regimen. CONCLUSIONS: The results of this observational study suggest that 5-HT3 receptor antagonists are no more effective than other commonly used medications in controlling postchemotherapy nausea and emesis in women with breast carcinoma who are treated with moderately emetogenic chemotherapy in community practice settings. In fact, they may be associated with significant prolongation of the course of postchemotherapy nausea.

Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain.

We conducted a study of the safety of controlled-release (CR) oxycodone tablets (OxyContin Tablets) administered chronically to patients with cancer-related pain in a usual clinical setting. These patients had participated in 1 of 2 double-blind, active-control studies. Our study was an open, 3-month treatment study that included 87 patients. Patients received CR oxycodone tablets every 12 hr in a manner that reflected typical clinical practice. Supplemental immediate-release (IR) oxycodone was available PRN for breakthrough pain. Patients recorded medication use, adverse events, and evaluations of pain intensity and acceptability of therapy in a daily diary. Forty-four patients (51%) completed all 12 weeks of study; 43 patients (49%) discontinued participation. At baseline and throughout the study period, the overall mean pain-intensity score was slight to moderate. A comparison of initial and final doses showed a significant but modest increase in total daily CR oxycodone dose. An increase or decrease in titration of the oxycodone dose occurred for 66 patients (84%) at least once during the 12-week study period, primarily for increased pain. Forty-four patients (56%) did not undergo dose titration when the latter was indicated. Half of the patients used IR oxycodone rescue almost daily; the mean number of rescue doses per day was 1.5. Despite stable pain control and an increasing total daily CR oxycodone dose, the percentage of patients reporting common opioid-related adverse events decreased over the course of the study. CR oxycodone tablets administered every 12 hr were successfully used to manage cancer pain over a 12-week period. Importantly, side effects diminished over time without a concomitant change in efficacy.

Anticipatory nausea and vomiting in the era of 5-HT3 antiemetics.

Cancer chemotherapy is known to lead to nausea and vomiting in a large proportion of cases. If emesis is severe it can lead in its turn to anticipatory nausea and vomiting (ANV), which cannot be controlled by antiemetic medication. The etiology of ANV and various methods that have been used to counteract the condition are discussed.

Effectiveness of a training program for enhancing therapists' understanding of the supportive-expressive treatment model for breast cancer groups.

This study evaluated a training program for leaders of supportive-expressive psychotherapy groups for breast cancer patients. Twenty-four mental health/medical cancer care professionals completed two training phases and were tested for their understanding of the treatment model. Participants' understanding was enhanced as a result of the training program. This study demonstrates that a brief training program can improve therapists' understanding of the treatment model and demonstrates an effective method of evaluation. Future research should examine how performance on these tests generalizes to performance when leading a supportive-expressive group.

Phase II study of goserelin for patients with postmenopausal metastatic breast cancer.

PURPOSE: To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE). PATIENTS AND METHODS: A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment. RESULTS: For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients. CONCLUSION: GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.

Combination hormone therapy for metastatic breast cancer. An ECOG study of megestrol and aminoglutethimide.

This study was performed to determine the toxicity and effectiveness of megestrol acetate used with aminoglutethimide-hydrocortisone in the treatment of patients with metastatic breast cancer. Forty-five patients were treated, 29 of whom were fully eligible. Twelve of the 45 who had diabetes and/or hypertension were also analyzed. All had measurable sites of disease. The median age was 63 years, and the median time from first recurrence to on-study was 19 months. Approximately half the patients already had chemotherapy, and about 90% had hormone therapy for advanced disease. The most common side effects were skin rash, weight gain, hyperglycemia, and renal and neurologic problems. No life-threatening or lethal toxicities were reported. The overall response rate (complete or partial) among the fully eligible patients was 34% (90% confidence intervals from 20% to 51%), with a 5-month median duration of response. Patients with soft tissue, visceral, and osseous disease responded. Seventy-two percent of fully eligible patients have progressed or relapsed. The median time to failure of treatment was 6 months, and the median survival time was 15 months.