Jatoi, A., Rowland, K., Sloan, J.A., Gross, H.M., Fishkin, P.A., Kahanic, S.P., . . . Loprinzi, C.L. (2008). Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: Results of a placebo-controlled trial from the North Central Cancer Treatment Group (N03CB). Cancer, 113, 847–853.
To compare the effectiveness of tetracycline 500 mg orally BID versus placebo for 28 days starting on day 1 of treatment with any epidermal growth factor receptor–inhibitor (EGFRI) agent to prevent or reduce EGFRI-induced rash in patients with cancer.
Patients were randomized to either the tetracycline arm (500 mg orally BID for 28 days) or the placebo arm.
This study was a collaborative effort of the North Central Cancer Treatment Group (including centers in Illinois, Iowa, Kansas, South Dakota, and Ohio) and the Mayo Clinic (Rochester, MN).
This was a placebo-controlled, doubled-blind trial.
Three patient-reported assessments were used.
Those three questionnaires were completed at baseline and weekly for eight weeks after initiation of tetracycline or placebo. Oncologists performed an evaluation at the end of four weeks and eight weeks. The evaluation included a history and physical examination, an assessment of patient performance status, and an assessment of adverse events (e.g., gastrointestinal toxicity, rash development) as per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Administration of tetracycline prophylactically did not significantly affect the incidence of rash development in patients receiving EGFRI drugs. Indicators suggest administration of tetracycline prophylactically may have a favorable influence with regard to rash severity in patients receiving EGFRI drugs. In addition, the results suggested these rashes bother patients, who must contend with itching, burning, and other types of skin irritation.
Jatoi, A., Kahanic, S.P., Frytak, S., Schaefer, P., Foote, R.L., Sloan, J., & Petersen, R.C. (2005). Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung cancer patients: Preliminary results and suggestions for future study designs. Supportive Care in Cancer, 13(1), 66–69.
The study was conducted to test oral donepezil and oral vitamin E in patients with small-cell lung cancer after completion of all cancer therapy and prophylactic cranial irradiation.
A randomization procedure was conducted after participant stratification in the following ways.
The treatment group received 5 mg/day of oral donepezil, which increased to 10 mg/day after one month of therapy if tolerated well. Treatment group participants also received 1000 IU/day of oral vitamin E. The control group was given an identical oral placebo. Assessments were performed at study enrollment, one month, and every three months until cancer recurrence or treatment failure.
The study took place at the North Central Cancer Treatment Group and the Mayo Clinic.
The study was a double-blind, placebo-controlled trial.
There were no notable differences in cognitive stability, adverse events, or quality of life between treatment arms. Only one patient, who received donepezil and vitamin E, manifested a three-point drop in cognitive scores as measured by the MMSE. There was a slight trend of increased gastrointestinal side effects among patients treated with donepezil and vitamin E.
The median time spent in the study was 42 or 69 days for the treatment or control group, respectively.
Due to low enrollment and retention, the effect of oral doses of vitamin E and donepezil on cognitive function could not be determined.
Jatoi, A., Windschitl, H.E., Loprinzi, C.L., Sloan, J.A., Dakhil, S.R., Mailliard, J.A., . . . Christensen, B. (2002). Dronabinol versus megestrol acetate versus combination therapy for cancer associated anorexia: A North Central Cancer Treatment Group study. Journal of Clinical Oncology, 20, 567–573.
To evaluate the efficacy of megestrol acetate versus dronabinol, as well as a combination of these treatments
This was a randomized, controlled, three-arm trial using a double-blind procedure. The first arm evaluated the efficacy of 800 mg/day of oral megestrol acetate plus a capsule placebo; the second arm evaluated the efficacy of 2.5 mg of oral dronabinol twice daily plus a liquid placebo; and the third arm combined both medications. Evaluations were taken at noted doses.
The final sample included 469 patients. The sample was stratified for confounding factors, including age, gender, cancer type, estimate of survival, performance status, severity of weight loss, concomitant radiation therapy, treatment center, and planned or ongoing treatment. Sample size calculations included a power analysis and accounted for attrition.
All participants shared the following characteristics:
North Central Cancer Treatment Group (NCCTG) trial involving 20 NCCTG institutions, including the Mayo Clinic
A double-blind, randomized controlled trial design was used.
No differences between groups at baseline were noted. A greater percentage of patients treated with megestrol acetate reported appetite improvement (75% versus 49%; p = 0.0001) and baseline weight gain (11% versus 3%, p = 0.02) for ≥ 10%) compared with dronabinol-treated patients. Combination treatment conferred no additional benefit.
FAACT demonstrated improved quality of life among megestrol acetate–treated and combination-treated patients. Uniscale scores were similar for both groups. Toxicity among groups was comparable, with the exception of a greater incidence of impotence among men who received megestrol acetate.
Jatoi, A., Rowland, K., Loprinzi, C.L., Sloan, J.A., Dakhil, S.R., MacDonald, N., . . . Christensen, B. (2004). An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer associated wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. Journal of Clinical Oncology, 22, 2469–2476.
To evaluate the efficacy of ecosapentaenoic acid (EPA) supplement plus placebo versus megestrol acetate plus placebo supplement versus combination of both EPA supplement and megestrol
The EPA dose was 1.09 g BID in supplement plus liquid placebo. The megesterol acetate dose was 600 mg/day plus placebo supplement BID. The combination dose was EPA 1.09 g supplement BID plus megesterol acetate 600 mg/day. Patients were stratified and randomized to one of three treatment arms. Median number of days on study was relatively equal for all three arms at slightly more than three months. Megesterol acetate served as the control arm secondary to its proven efficacy.
The study was a collaborative effort of the North Central Cancer Treatment Group (NCCTG) and the National Cancer Institute of Canada, conducted at 26 primary treatment centers.
A double-blinded, randomized, three-armed trial design was used.
The primary endpoint was weight gain of 10% or more (chosen because of previously proven efficacy of megesterol acetate). Among the three arms, 6% of patients achieved this in the EPA arm, 18% in the megesterol arm, and 11% in the combination arm. There was a p value of 0.01 showing greater efficacy with single-agent megesterol acetate. Appetite results using the NCCTG questionnaire were comparable for all three groups, showing varying degrees of favorable effects in all treatment arms. Appetite results using FAACT showed that the megesterol acetate and combination arms provided better appetite stimulation than EPA alone: 40 for EPA, 55 for megesterol acetate, and 55 for combination.
There was no significant difference for survival times or quality of life between the three arms. Recommendation of authors is not to use EPA alone or in combination.
Sample size was very good, and statistical analysis was very thorough.
Jatoi, A., Thrower, A., Sloan, J.A., Flynn, P.J., Wentworth-Hartung, N.L., Dakhil, S.R., . . . Loprinzi, C.L. (2010). Does sunscreen prevent epidermal growth factor receptor (EGFR) inhibitor-induced rash? Results of a placebo-controlled trial from the North Central Cancer Treatment Group (N05C4). Oncologist, 15, 1016–1022.
To determine whether sunscreen prevents or mitigates epidermal growth factor receptor–inhibitor (EGFRI)-induced rashes.
Patients were stratified based on (a) first-line cancer therapy versus other therapy, (b) type of EGFRI prescribed or anticipated (e.g., small molecule inhibitor versus monoclonal antibody), and (c) use of a concurrent medication that increases sun hypersensitivity.
Patients were randomly assigned to sunscreen with a sun protection factor (SPF) of 60 to be applied to the face, trunk, and extremities BID for 28 days versus an identical-appearing placebo. The sunscreen included 7.5% titanium dioxide and 7.5% zinc oxide, and was shown to block more than 90% of both ultraviolet A and ultraviolet B light in preclinical trials. All patients were instructed to stay indoors or in a covered area from 10 AM to 3 PM to avoid peak sun exposure.
Patients were undergoing the active treatment phase of care.
This was a placebo-controlled, double-blind trial.
The use of sunscreen (SPF of 60) did not prevent or decrease the severity of EGFRI-induced rash.
No evidence existed to support the use of sunscreen to prevent or decrease the severity of EGFRI-induced rash.
Jassim, G.A., Whitford, D.L., Hickey, A., & Carter, B. (2015). Psychological interventions for women with non-metastatic breast cancer. Cochrane Database of Systematic Reviews, 5, CD008729.
STUDY PURPOSE: To evaluate evidence for psychological interventions in women with breast cancer
TYPE OF STUDY: Meta analysis and systematic review
PHASE OF CARE: Multiple phases of care
In 24 of 28 trials, cognitive behavioral therapy was the basis of the intervention. Most studies had unclear risk of bias, and for studies aimed at anxiety and depression, quality of the evidence was graded as low. Comparison of CBT versus control across multiple studies for depression showed an overall standard mean difference (SMD) of -1.01 (p = 0.02) in favor of the CBT intervention. Only two studies examined CBT delivered individually, showing no significant benefit and high heterogeneity. Examined separately, group CBT also did not consistently show significant benefit for depression. Eight studies looked at change in anxiety. Both individual- and group-delivered CBT showed significant benefit, with an overall SMD -10.48 (p = 0.0006). CBT showed a significant positive effect for stress, and only marginal effect on quality of life.
Findings showed overall benefit of CBT for anxiety and depression in women with early-stage breast cancer
Although studies have shown that psychological interventions are more effective for individuals with psychological problems, the studies included here excluded women with psychological morbidity. There was high heterogeneity, and most studies were of low quality.
CBT delivered in a group or individual setting has been shown to have a positive effect on depression and anxiety among women with early-stage breast cancer. The strength of these results is limited by the relatively low quality of studies included in this review.
Janusch, M., Fischer, M., Marsch, W., Holzhausen, H.J., Kegel, T., & Helmbold, P. (2006). The hand-foot syndrome—A frequent secondary manifestation in antineoplastic chemotherapy. European Journal of Dermatology, 16, 494–499.
Multiple interventions can be implemented to prevent or minimize PPE, including teaching patients to avoid mechanical irritation of the skin, use topical emollient creams, and use regional cooling.
Jantunen, E., Kuittinen, T., & Nousiainen, T. (2002). A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients. Leukemia and Lymphoma, 43, 1961–1965.
The study was conducted between November 1998 and February 2000.
This was a pilot, feasibility study.
The National Cancer Institute (NCI) Common Toxicity Criteria for Oral Mucositis was used to assess oral mucositis daily.
Most of the patients (9 out of 10) received the full dose of amifostine. One patient received only 780 mg/m2 because of recurrent hypotension. Significant nausea, as well as hypotension and vomiting, occurred.
Amifostine did not show a benefit for gastrointestinal toxicity or mucositis of more than grade 2.
Jang, G., Song, H.H., Park, K.U., Kim, H.S., Choi, D.R., Kwon, J.H., . . . Zang, D.Y. (2013). A phase II study to evaluate the efficacy of ramosetron, aprepitant, and dexamethasone in preventing cisplatin-induced nausea and vomiting in chemotherapy-naive cancer patients. Cancer Research and Treatment, 45(3), 172–177.
To evaluate the efficacy of ramosetron, aprepitant, and dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy
On day 1, all patients received intravenous 0.6 mg ramosetron and oral 12 mg dexamethasone 30 minutes before chemotherapy, and they received 125 mg aprepitant orally one hour before chemotherapy. On days 2 and 3, patients received 80 mg aprepitant and 8 mg dexamethasone orally in the morning. On day 4, patients only received 8 mg dexamethasone. Patients could take rescue antiemetic medications at any time for vomiting or severe nausea. Antiemetic rescue medications were determined by treating physicians.
Prospective, open-label study
Complete response (CR) was achieved by 94.9% of patients in the acute phase, 92.3% in the delayed phase, and 92.3% in the overall phase. Absolute CR was achieved by 74.4% in the acute phase, 51.3% in the delayed phase, and 46.2% in the overall phase. The median nausea score during the acute phase was 0 (interquartile range [IQR] 0–1), 0 in the delayed phase (IQR 0–4), and 2 during the overall phase (IQR 0–4). On the VAS, mild nausea was observed in 10% of patients in the acute phase and 13% of patients in the delayed phase. Moderate to severe nausea was observed in 15% of patients in the acute phase and 36% of patients in the delayed phase.
The combination of ramosetron, aprepitant, and dexamethasone is an effective CINV regimen. The overwhelming majority of patients in this study achieved a complete response and experienced no nausea or vomiting in both the acute and delayed phase after chemotherapy.
Ramosetron, aprepitant, and dexamethasone is an effective regimen to prevent CINV in patients receiving cisplatin-based therapy. Almost all of the patients were able to achieve a complete response in both the acute and delayed phase after administration of chemotherapy. In this study, the majority of patients were receiving palliative care, therefore this combination of drugs should be considered for palliative care patients.
Janelsins, M.C., Peppone, L.J., Heckler, C.E., Kesler, S.R., Sprod, L.K., Atkins, J., . . . Mustian, K.M. (2015). YOCAS©® Yoga reduces self-reported memory difficulty in cancer survivors in a nationwide randomized clinical trial: Investigating relationships between memory and sleep. Integrative Cancer Therapies, 15, 263–271.
To investigate the effect of a combined hatha and restorative yoga intervention on memory in cancer survivors and to explore relationships between memory and sleep
YOCAS©® (Yoga for Cancer Survivors) is an instructor-guided standardized program that incorporates movement emphasizing restorative poses, breathing exercises, and mindfulness exercises. The intervention was offered twice a week in the late afternoon or evening over 75 minutes for a total of eight sessions. Although all the group trainers were Registered Yoga Alliance Teachers, they were also required to complete a training session, reviewing a detailed YOCAS©® manual to facilitate standardization across sites.
PHASE OF CARE: Late effects and survivorship
Secondary analysis of a randomized, clinical trial
At baseline, the average score on the MDASI indicated only a mild level of perceived memory problems overall. Although both groups continued to report memory problems as being mild, a significant decrease (p < 0.05) was observed in patients who completed the intervention. This difference continued to be significant when controlling for differences in age, gender, educational level, past treatment regimen, current hormonal therapy, baseline memory, and baseline sleep scores. Of note, those who received the intervention also had improved sleep (p < 0.05), which accounted for approximately 26% of the improvement in memory (p = 0.039).
Although yoga appeared to decrease perceived memory problems, this outcome was based on a single item of the MDASI. Further longitudinal studies designed specifically to measure the effect of yoga on cognitive function as measured by both objective and subjective measures are warranted.
Although this study suggested that yoga may improve patients’ perception of memory problems, some of the benefit was because of better sleep.