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.

The n-of-1 clinical trial: the ultimate strategy for individualizing medicine?

N-of-1 or single subject clinical trials consider an individual patient as the sole unit of observation in a study investigating the efficacy or side-effect profiles of different interventions. The ultimate goal of an n-of-1 trial is to determine the optimal or best intervention for an individual patient using objective data-driven criteria. Such trials can leverage study design and statistical techniques associated with standard population-based clinical trials, including randomization, washout and crossover periods, as well as placebo controls. Despite their obvious appeal and wide use in educational settings, n-of-1 trials have been used sparingly in medical and general clinical settings. We briefly review the history, motivation and design of n-of-1 trials and emphasize the great utility of modern wireless medical monitoring devices in their execution. We ultimately argue that n-of-1 trials demand serious attention among the health research and clinical care communities given the contemporary focus on individualized medicine.

Factors affecting survival among women with breast cancer in Hawaii.

BACKGROUND: Given previous reports of ethnic differences in breast cancer survival among Hawaii's 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.

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/m IV over 60 minutes day 1, followed by 5-FU 500 mg/m IV bolus and LV 200 mg/m IV over 60 minutes day 2, followed by oral LV 15 mg every 6 hours x 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.

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 Noni's popularity, there is a lack of standardization of products and no scientific evidence of Noni's 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.

Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a Southwest Oncology Group study.

From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m(2) of 5-FU, 500 mg/m(2) of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines.

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.

Exercise and side effects among 749 patients during and after treatment for cancer: a University of Rochester Cancer Center Community Clinical Oncology Program Study.

GOALS: Despite advances in cancer treatment and symptom management, many patients experience side effects from cancer treatments that cause suffering and impair quality of life (QOL). Exercise is a method for enhancing QOL among cancer patients that shows promise in reducing side effects. However, patient participation in exercise is not well defined. We report on exercise participation during and within 6 months after chemotherapy and radiation therapy, the association of exercise with treatment side effects, and the communication between physicians and patients about exercise in a large (N = 749) nationwide sample of cancer patients. PATIENTS AND METHODS: Participants completed measures that included questions concerning exercise during and after treatment, treatment side effects, and communication with physicians regarding exercise. Questionnaires were administered 2 weeks and 6 months after completion of therapy. RESULTS: Almost half of the 749 participating patients reported exercising while undergoing chemotherapy and/or radiation, and more than half reported exercising during the 6 months after treatment. Exercise was associated with less severe side effects during and after treatment (p < or = 0.050). More than 30% of patients reporting exercise did not discuss exercise with a physician; however, those who did were more likely to talk with their oncologist than with their primary care provider. CONCLUSIONS: Cancer patients report exercising and appear amenable to attempting exercise during and within 6 months after treatment. Research is needed to assess (1) the frequency, intensity, duration, and mode of exercise; (2) randomized controlled trials with exercise and its influence on treatments and side effects; and (3) physician-patient communication regarding exercise during cancer treatment.

Breast cancer treatment among women of different ethnicity in Hawaii.

BACKGROUND: An analysis of breast cancer survival for Hawaii's multiethnic women in the 1970s and 1980s showed that Hawaiian and Filipino women experienced a worse survival than their Caucasian and Japanese counterparts even after controlling for stage at diagnosis. We conducted this study to test for ethnic differences in treatment compliance with established guidelines while adjusting for stage at diagnosis and other disease characteristics. METHODS: A total of 406 newly diagnosed breast cancer patients identified through the Hawaii Tumor Registry were available for this project. Two hundred fifty-nine patients of the sample were from Hawaii's predominant fee-for-service multiple private office/community hospital setting and 147 patients were members of a Health Maintenance Organization (HMO). The primary measures assessed were treatment received, ethnicity, age at diagnosis, cancer stage, hormone receptor status, comorbidity, and treatment toxicities. Physician's Data Query (PDQ) guidelines were used as the standard of care. We examined whether there were ethnic-related differences in compliance with PDQ treatment guidelines according to stage at diagnosis. RESULTS: Overall, 25 percent of the sample did not receive treatment that was specifically recommended by PDQ guidelines and 7 percent received treatment that was not recommended by PDQ for the patients' stage of disease. There were no statistically significant ethnic-related differences in compliance with PDQ guidelines. Although not statistically significant, Caucasians and Japanese were less likely than other groups to receive axillary lymph node sampling/dissection and Chinese were more likely than other groups to receive chemotherapy when it was not specifically recommended by the PDQ. There was no difference in adherence to PDQ guidelines between the sample treated in a fee-for-service setting and the sample treated by the HMO. Hawaiians and Chinese experienced lower levels of Grade 3 and 4 chemotherapy-related toxicities than other groups. CONCLUSION: The results of this study do not suggest that treatment compliance with established guidelines differs by ethnicity. Our unexpected finding that Hawaiian and Chinese women experienced lower levels of Grade 3 and 4 chemotherapy-related toxicities deserves further investigation.

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.

Prevalence of complementary and alternative medicine use in cancer patients during treatment.

GOALS OF WORK: To assess complementary and alternative medicine (CAM) therapies being utilized by cancer patients during treatment and communication about CAM usage between the patient and physician. PATIENTS AND METHODS: Newly diagnosed cancer patients receiving chemotherapy or radiation therapy were recruited to complete a CAM survey within 2 weeks after the termination of treatment. Patients were queried on which CAM modalities they utilized and whether or not they were discussed with either their oncologist or primary care physician. MAIN RESULTS: Of the patients surveyed, 91% reported using at least one form of CAM. The most widely used forms of CAM were prayer, relaxation and exercise. CAM users tended to be women chemotherapy patients with at least a high school education. Of the patients using CAM, 57% discussed the use of at least one of these therapies with their oncologist or primary care physician. The most frequent CAM modalities discussed with at least one physician were diets, massage, and herbal medicine. CONCLUSIONS: An overwhelming proportion of cancer patients are using CAM, particularly prayer, relaxation, and exercise. However, patients may not discuss the use of CAMs at all or fully with their physician; if they do, it is most likely to be their oncologist, but not about the most frequently used CAMs. Future research needs to assess effective ways for oncologists to gather information about CAM usage by patients during allopathic treatment and discern ways these therapies may enhance or interfere with traditional cancer treatments.

Influences of ethnicity, treatment, and comorbidity on breast cancer survival in Hawaii.

The purpose of this study was to examine factors contributing to the ethnic discrepancies in breast cancer survival described previously. Through the use of the Hawaii Tumor Registry and insurance claims data, 1,052 breast cancer patients' survival times were examined in relation to demographics, disease characteristics, comorbidity, and treatment patterns as compared to national guidelines for breast cancer treatment. In stepwise and hierarchical Cox regression models, TNM stage was the strongest predictor of survival and explained all of the ethnic survival differences. In addition, comorbidity and treatment patterns were significant in predicting survival. In this population of health plan members, ethnic differences in survival were not a result of differential treatment, but due to variations in early detection. These results support the hypothesis that pre-existing conditions and treatment patterns are related to breast cancer survival even after controlling for stage at diagnosis indicating the usefulness of insurance claims data in this research field.

The use of breast conserving surgery: linking insurance claims with tumor registry data.

BACKGROUND: The purpose of this study was to use insurance claims and tumor registry data to examine determinants of breast conserving surgery (BCS) in women with early stage breast cancer. METHODS: Breast cancer cases registered in the Hawaii Tumor Registry (HTR) from 1995 to 1998 were linked with insurance claims from a local health plan. We identified 722 breast cancer cases with stage I and II disease. Surgical treatment patterns and comorbidities were identified using diagnostic and procedural codes in the claims data. The HTR database provided information on demographics and disease characteristics. We used logistic regression to assess determinants of BCS vs. mastectomy. RESULTS: The linked data set represented 32.8% of all early stage breast cancer cases recorded in the HTR during the study period. Due to the nature of the health plan, 79% of the cases were younger than 65 years. Women with early stage breast cancer living on Oahu were 70% more likely to receive BCS than women living on the outer islands. In the univariate analysis, older age at diagnosis, lower tumor stage, smaller tumor size, and well-differentiated tumor grade were related to receiving BCS. Ethnicity, comorbidity count, menopausal and marital status were not associated with treatment type. CONCLUSIONS: In addition to developing solutions that facilitate access to radiation facilities for breast cancer patients residing in remote locations, future qualitative research may help to elucidate how women and oncologists choose between BCS and mastectomy.