Brian F. Issell

Acupuncture-point stimulation for chemotherapy- induced nausea and vomiting

PURPOSE Assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. MATERIALS AND METHODS Randomized trials of acupuncture-point stimulation by needles, electrical stimulation, magnets, or acupressure were retrieved. Data were provided by investigators of the original trials and pooled using a fixed-effects model. RESULTS Eleven trials (N = 1,247) were pooled. Overall, acupuncture-point stimulation reduced the proportion of acute vomiting (relative risks [RR] = 0.82; 95% CI, 0.69 to 0.99; P = .04), but not the mean number of acute emetic episodes or acute or delayed nausea severity compared with controls. By modality, stimulation with needles reduced the proportion of acute vomiting (RR = 0.74; 95% CI, 0.58 to 0.94; P = .01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% CI, 0.60 to 0.97; P = .02), but manual acupuncture did not; delayed symptoms were not reported. Acupressure reduced mean acute nausea severity (standardized mean difference = -0.19; 95% CI, -0.38 to -0.01; P = .03) and most severe acute nausea, but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. CONCLUSION This review complements data on postoperative nausea and vomiting, suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies with state-of-the-art antiemetics as well as studies for refractory symptoms are needed to determine clinical relevance. Acupressure seems to reduce chemotherapy-induced acute nausea severity, though studies did not involve a placebo control. Noninvasive electrostimulation seems unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Mitomycin: ten years after approval for marketing.

Mitomycin was approved for marketing by the Food and Drug Administration in 1974 for use in gastric and pancreatic carcinomas when combined with other chemotherapeutic agents. Since then, mitomycin has been used extensively in combination chemotherapy for a variety of tumors, particularly in the past seven years. However, the contribution of this agent to the various drug regimens has not been adequately defined. Clear evidence of the drugs activity as a single agent has been seen in the intravesical treatment of superficial bladder carcinoma. Common toxicities include anorexia, vomiting, and myelosuppression. Less common, but potentially lethal, toxicities in the form of fibrosing alveolitis and microangiopathic hemolytic anemia with renal failure are being reported with increasing frequency. These potentially severe adverse effects, coupled with the still undefined role of mitomycin in systemic cancer chemotherapy, suggest that selection of this drug for other than investigational use should be made with care.

Phase 1 Trial of Recombinant Human Interleukin-1β (rhIL-1β), Carboplatin, and Etoposide in Patients with Solid Cancers: Southwest Oncology Group Study 8940

Recombinant human interleukin-1β (rhIL-1β) was evaluated in a phase 1 Clinical Trial in which patients with metastatic or unresectable solid tumors received carboplatin and etoposide in cycle 1 and carboplatin, etoposide, and rhIL-1β in cycle 2. Recombinant hIL-1β was given intravenously for 5 days in one of three schedules: (1) immediately postchemotherapy, (2) delayed for 5 days after chemotherapy, or (3) concurrently with chemotherapy. Four dose levels of rhIL-1β were evaluated: 20, 50, 100, and 200 ng/kg. The doses of carboplatin and etoposide were not changed between cycle 1 and cycle 2 so that the effect ofrhlL-1β on chemotherapy-induced hematotoxicity was evaluated; 54 patients were entered on study and 42 patients received at least two cycles of therapy and were thus evaluablefor rhIL-1β toxicity and for the effect ofrhIL-1β on hematotoxicity of carboplatin andetoposide. The major toxicities of rhIL-1β were chills, rigors, headache, fatigue, and hypotension. The maximum tolerated dose of rhIL-1β w...

Exploratory analysis of the usefulness of acupressure bands when severe chemotherapy-related nausea is expected.

The present study examines the efficacy of acupressure wristbands, compared with standard care alone and acustimulation wristbands, in preventing severe nausea among 86 breast cancer patients receiving doxorubicin-based chemotherapy who were at high risk of experiencing severe nausea following treatment. Significant differences in the proportion of patients who reported severe nausea were observed across three conditions (standard care, standard care with acupressure bands, and standard care with an acustimulation band). The proportion of patients in the acupressure band group who reported severe nausea following their chemotherapy treatment (41%) was significantly less than that of the standard care group (68%) and the acustimulation band group (73%). Overall, these findings showed that acupressure wristbands were efficacious and may be an appropriate form of adjuvant therapy for nausea management for breast cancer patients, especially those who are most at risk for experiencing severe nausea following chemotherapy treatment.

Complementary and alternative medicine use and breast cancer prognosis: a pooled analysis of four population-based studies of breast cancer survivors.

BACKGROUND Complementary and alternative medicine (CAM) use is common among breast cancer survivors, but little is known about its impact on survival. METHODS We pooled data from four studies conducted in Hawaii in 1994-2003 and linked to the Hawaii Tumor Registry to obtain long-term follow-up information. The effect of CAM use on the risk of breast cancer-specific death was evaluated using Cox regression. RESULTS The analysis included 1443 women with a median follow-up of 11.8 years who had a primary diagnosis of in situ and invasive breast cancer. The majority were Japanese American (36.4%), followed by white (26.9%), Native Hawaiian (15.9%), other (10.6%), and Filipino (10.3%). CAM use was highest in Native Hawaiians (60.7%) and lowest in Japanese American (47.8%) women. Overall, any use of CAM was not associated with the risk of breast cancer-specific death (hazard ratio [HR] 1.47, confidence interval [CI] 0.91-2.36) or all-cause death (HR 0.82, 95% CI 0.63-1.06). However, energy medicine was associated with an increased risk of breast cancer-specific death (HR 3.19, 95% CI 1.06-8.52). When evaluating CAM use within ethnic subgroups, Filipino women who used CAM were at increased risk of breast cancer death (HR 6.84, 95% CI 1.23-38.19). CONCLUSIONS Our findings suggest that, overall, CAM is not associated with breast cancer-specific death but that the effects of specific CAM modalities and possible differences by ethnicity should be considered in future studies.

Factors Affecting Survival Among Women with Breast Cancer in Hawaii

BACKGROUND Given previous reports of ethnic differences in breast cancer survival among Hawaiis population, we investigated the role of adherence to treatment standards, treatment toxicity, preexisting chronic conditions, and obesity in the survival of 382 prospectively studied breast cancer patients representing six ethnic groups. METHODS Participants were recruited from several hospitals in Honolulu. Information on tumor characteristics and treatment was abstracted from medical records. Based on the Physicians Data Query (PDQ®), we assessed compliance with recommended treatment guidelines. Vital status and cause of death data were obtained through linkage with the Hawaii Tumor Registry. Cox proportional hazard models were used to compute hazard ratios for predictors of survival. RESULTS After a median follow-up time of 13.2 ± 3.7 years, 115 deaths had occurred, 43 from breast cancer and 72 from other causes. After adjustment, we observed only small differences in survival by ethnicity that were not statistically significant. In addition to advanced disease stage, obesity at diagnosis was a significant independent predictor of worse and receiving PDQ-recommended treatment of better breast cancer-specific and all-cause survival. Developing high-grade toxicity was associated with worse breast cancer survival, whereas comorbidity and older age at diagnosis were associated with higher all-cause mortality. Hormone receptor status, menopausal status, and type of health insurance were not associated with survival. CONCLUSIONS These findings suggest that given access to healthcare, breast cancer patients experience similar survival rates. Although more information about mechanisms of action would be useful, it appears reasonable to recommend weight control to breast cancer survivors.

Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients With Advanced Cancer to Select a Phase II Dose

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6–8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

Pharmacokinetic study of Noni fruit extract.

Many different products containing Noni (Morinda citrifolia) fruit extracts are sold throughout the world for health restoration and maintenance. Despite a large business enterprise fueling Nonis popularity, there is a lack of standardization of products and no scientific evidence of Nonis clinical efficacy and safety. There is also no evidence to indicate an optimal therapeutic dose or dosing interval. In an initial volunteer, scopoletin was identified as a bioactive marker of Noni exposure and a candidate for product standardization and pharmacokinetic studies. Subsequently, capsules containing the whole freeze-dried fruit of Noni were orally administered to nine healthy volunteers (3 per group) at doses of 1,500 mg (3 × 500 mg), 2,000 mg (4 × 500 mg) and 2,500 mg (5 × 500 mg). Plasma and urine samples were obtained from each subject prior to dosing and at 0.5, 1, 2, 4 and 8 h after dosing. Concentrations of scopoletin were determined by HPLC with PDA (scanning at 200–700 nm) and MS detection. Scopoletin rapidly enters the plasma after Noni ingestion, maintaining levels in the range of 0.5 to 5 ng/mL for at least 8 h after dosing. Scopoletin bioavailability appears to be low, with significant intersubject variability. We conclude that scopoletin can be used as a relatively specific marker of Noni exposure in the blood and particularly in urine when its pharmacokinetics is considered appropriately.

S9511: a Southwest Oncology Group phase II study of trimetrexate, 5-fluorouracil, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach.

Objective:The primary objective of this trial was to evaluate the response rate for trimetrexate in conjunction with 5-FU and leucovorin (LV) (= TFL) in the treatment of advanced gastric cancer in a phase II, cooperative group setting. Methods:Patients with locally advanced, unresectable, or metastatic adenocarcinoma of the stomach received trimetrexate 110 mg/m2 IV over 60 minutes day 1, followed by 5-FU 500 mg/m2 IV bolus and LV 200 mg/m2 IV over 60 minutes day 2, followed by oral LV 15 mg every 6 hours × 7 doses, all weekly for 6 weeks followed by 2 weeks of rest, continued until progression. Results:Characteristics for 37 eligible patients: median age 63 (range: 23–83); male/female: 69% of 31%; performance status 0/1/2 15/20/1. The confirmed response rate was 19%, and median overall survival was 6 months. Two patients died as a result of therapy, 1 because of infection without significant neutropenia, and 1 due to perforation of a responding gastric lesion. Seventy-two percent experienced grades 3 and 4 toxicity, most commonly diarrhea, fatigue, and lymphopenia. Conclusions:This regimen achieves response rates comparable to other 5-FU-based regimens, when used in treatment of incurable gastric cancer. Toxicity appears manageable.