Mantovani, G., Macciò, A., Madeddu, C., Gramignano, G., Serpe, R., Massa, E., . . . Floris, C. (2008). Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results. Nutrition, 24, 305–313.
All patients received basic treatment with polyphenols (300 mg/day) from alimentary sources (e.g., onions, apples, oranges, red wine, and green tea) or supplementary tablets. Patients also received antioxidant agents (a-lipoic acid and carbocisteine), as well as vitamins A, C, and E, orally. All patients then were randomized to one of the following five treatment arm interventions:
The planned treatment duration was four months. Patient outcomes were evaluated at 4, 8, 16, and 24 weeks.
Policlinico Universitario and Ospedale Oncologico Regionale, Cagliari, Italy
The study was a randomized, phase II, two-center clinical trial with five treatment arms.
Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)
When comparing baseline and posttreatment measures, statistically significant improvements in fatigue outcomes were observed in the L-carnitine treatment arm (p = 0.039) and the MPA/MA plus pharmacologic nutritional support, L-carnitine, and thalidomide arm (p = 0.015). Fatigue worsened significantly in patients receiving EPA-enriched oral supplementation treatment (p = 0.051).
Mantovani, G., Maccio, A., Madeddu, C., Serpe, R., Massa, E., Dessi, M., . . . Contu, P. (2010). Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist, 15, 200–211.
To determine the most effective and safest treatment to improve primary endpoints of lean body mass, resting energy expenditure, and fatigue in patients with cancer-related anorexia-cachexia syndrome
To determine the effects on secondary endpoints of appetite, quality of life, grip strength, Glasgow Prognostic Score, and proinflammatory cytokines
All patients were given the following standard treatment orally via pills or dietary intake:
Patients were randomly assigned to one of the following five treatment arms:
Planned treatment duration was four months.
The multisite study was conducted in Italy.
The study was a phase III, prospective, randomized trial.
Results demonstrate efficacy of a combined treatment approach in cancer cachexia syndrome.
Results seem to confirm that cancer cachexia, as a multidimensional syndrome, is likely to yield success with a multifactorial approach.
Results appear to confirm thinking that cachexia is driven by inflammatory cytokines and that drugs that down-regulate the production and/or release of proinflammatory cytokines can be effective in reversing the symptoms of the syndrome.
It is noted that the drugs and dietary supplements used are low cost.
Combined treatments used here may indicate an additive or synergistic effect of the agents.
Mansouri, P., Haghighi, M., Beheshtipour, N., & Ramzi, M. (2016). The effect of aloe vera solution on chemotherapy-induced stomatitis in clients with lymphoma and leukemia: A randomized controlled clinical trial. International Journal of Community Based Nursing and Midwifery, 4, 119–126. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876780
To assess the effect of aloe vera solution on stomatitis and its pain intensity in patients undergoing chemotherapeutic procedures
In a randomized, controlled clinical trial, 64 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) undergoing chemotherapy were randomly divided into a control and intervention group. The intervention group was asked to wash their mouths with 5 mls of aloe vera solution for two minutes twice a day for 14 days. The control group used the ordinary mouthwashes recommended in hematologic centers.
PHASE OF CARE: Active antitumor treatment
Randomized, controlled clinical trial patients were randomly divided into a control and an intervention group.
Aloe vera solution mouthwash significantly reduced the intensity of stomatitis and its pain in the intervention group compared to the control group. On day one, no difference existed; on the other days, there was a significant difference (days 3–14: p = 0.001 for stomatitis intensity, p = 0.001 for pain).
Aloe vera solution might improve patients’ nutritional status, reduce stomatitis and its pain intensity, and lead to satisfaction.
Aloe vera mouthwash can be useful in preventing and treating stomatitis in patients with chemotherapy-induced stomatitis without any side effects.
Mansouri, A., Hadjibabaie, M., Iravani, M., Shamshiri, A. R., Hayatshahi, A., Javadi, M. R., et al. (2011). The effect of zinc sulfate in the prevention of high-dose chemotherapy-induced mucositis: A double-blind, randomized, placebo-controlled study. Hematological Oncology, 30, 22-26.
Evaluate the effect of oral zinc sulfate for prevention of chemotherapy-induced oral mucositis in patients undergoing hematopoietic stem cell transplantation (HSCT).
Zinc sulfate at 440 mg/day provided orally in two doses every 12 hours, or placebo was provided beginning the day before starting the conditioning regimen. The capsules were administered by hospital staff. Patients were followed every day. All patients received the same prophylaxis regimen, which included 20 drops nystatin every three hours, chewable sucralfate 500 mg every eight hours, and mouthwashes such as chlorhexidine, amphotericin, and diluted povidone iodine every three hours.
The study was comprised of 60 patients, with a mean age 30.87 and 27.13 years per group.
Female 30%, Male 70%
All patients were receiving conditioning regimens for HSCT.
Single site, inpatient setting, Tehran, Iran
Randomized, double blind, placebo controlled
WHO mucositis grading scale
There were no significant differences between groups in mucositis grade, time of onset, or duration.
Zinc sulfate did not show any benefit for the prevention and management of oral mucositis.
Small sample <100
Findings suggest that oral zinc sulfate is not beneficial for oral mucositis induced by high-dose chemotherapy for patients undergoing HSCT. Efficacy of zinc sulfate in other patient populations is not clear.
Mann, E., Smith, M. J., Hellier, J., Balabanovic, J. A., Hamed, H., Grunfeld, E. A., & Hunter, M. S. (2012). Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomised controlled trial. Lancet Oncology, 13, 309–318.
To investigate whether cognitive-behavioral therapy (CBT) can help survivors of breast cancer in effectively managing menopausal symptoms.
The intervention consisted of six 90-minute weekly sessions with group discussions, handouts, weekly homework, and paced breathing and relaxation practice—along with an audio CD to practice paced breathing and relaxation at home daily—in addition to usual care. The control group received usual care and follow-up by an oncologist or clinical nurse specialist every six months. Assessments took place at baseline, nine weeks after randomization (typically two weeks after treatment), and 26 weeks after randomization. All sessions were audio recorded, and a 10% random sample of the tapes was reviewed to evaluate the intervention.
This was a triple-blinded, randomized, controlled trial.
Night sweats problem rating scores at 9 and 26 weeks were lower in the CBT group than they were in the usual care group, with a mean difference between groups of –1.67 (95% confidence interval [CI] [–2.43, –0.91]; p < .0001). These scores also declined over time in the control group. There were no differences between groups in hot flush frequency, night sweats frequency, or SSC measures. Those receiving the CBT intervention reported less sleep problems (adjusted mean difference (AMD) = –0.16; 95% CI [–0.29, –0.02]), anxiety (AMD = –0.16; 95% CI [–0.29, –0.02]), and better memory and concentration (AMD = –0.14; 95% CI [–0.26, –0.02]).
The findings suggest that group CBT improved patients’ perceptions of the degree to which hot flashes were a problem but did not appear to affect the actual frequency or objective measures of hot flashes. Group CBT appeared to have a small size of effect on sleep problems, anxiety, and other self-reported outcomes.
This study provides some supportive evidence for the benefit of cognitive-behavioral approaches. Group CBT may have a benefit in managing hot flashes and other symptoms through altered perceptions of the degree to which these symptoms are seen as problematic. Health professionals, such as breast cancer nurses or clinical nurse specialists trained in CBT, can improve long-term health outcomes for patients with breast cancer, and CBT could be incorporated into breast cancer survivorship programs.
Mannix, C.M., Bartholomay, M.M., Doherty, C.S., Lewis, M., & Bilodeau, M.L. (2012). A feasibility study of low-cost, self-administered skin care interventions in patients with head and neck cancer receiving chemoradiation. Clinical Journal of Oncology Nursing, 16(3), 278–285.
To evaluate a low-cost, patient-administered skin care regimen for minimizing skin toxicities in patients with head and neck cancer receiving chemoradiation
A skin care algorithm was created that included a radiation dermatitis assessment (subjective and objective data and pertinent medical history); a skin toxicity grading; and the management of skin toxicities based on patients' grades. Patients were given laminated cards with specific skin care instructions and were provided with verbal instructions. Teaching included: wash daily with mild soap (e.g., Dove) and warm water TID; be gentle (do not scrub); pat skin dry; apply Aveeno® moisturizer to skin in treated area; do not apply lotions within four hours of radiation treatment; keep skin moist; keep well hydrated; maximize nutrition; provide loose clothing; avoid friction; and protect skin from sun (e.g., sunscreen with SPF 30 and lip balm with sunscreen). For skin toxicities of grade 2 or higher, a consult was made to a clinical nurse specialist with consideration for a consult to a burn clinic for alternative skin products. Data were collected at baseline and at weekly intervals. At least three clinicians reviewed and compared both the National Cancer Institute (NCI) grades and digital photographs to reach 100% inter-rater agreement.
Prospective, descriptive study design
Investigators developed a demographic data collection form and a weekly skin care diary. Skin grading was assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE v3.0) grading scale for dermatitis associated with chemoradiation.
The verbal instructions and laminated skin care instructions provided to the subjects in this study proved to be an affordable regimen to which patients could easily adhere. These interventions, combined with increased patient–provider interaction at weekly assessments, most likely contributed to the high level of adherence.
Nurses can promote positive patient outcomes through proactive patient education, the early initiation of a skin care regimen, and the ongoing reinforcement of skin care interventions that may be beneficial in minimizing skin toxicities. Empowering patients to become active participants in their care may also contribute to positive outcomes. It is within nursing scope-of-practice to provide educational cards to patients for education and to promote skin care during treatment.
Manne, S.L., Winkel, G., Rubin, S., Edelson, M., Rosenblum, N., Bergman, C., . . . Rocereto, T. (2008). Mediators of a coping and communication-enhancing intervention and a supportive counseling intervention among women diagnosed with gynecological cancers. Journal of Consulting and Clinical Psychology, 76, 1034–1045.
To implement two psychological interventions to evaluate the effects of coping and communication-enhancing intervention (CCI) and supportive counseling (SC) on depressive symptoms.
Subjects were randomized into three groups based on Beck Depression Inventory (BDI) baseline score. CCI and SC groups consisted of six individual sessions of one-hour each plus one telephone session one week after the sixth individual session. There was a pre-intervention baseline questionnaire, and measures were repeated three times—at three months, six months, and nine months. Data were collected over six years, but each participant was involved for only the nine months of repeated measures.
There were no significant differences in depressive symptoms in any group over time or at any point in time. Depressive symptoms declined in all groups over time. Compared with UC, people in the CCI group showed significant effect interventions on BDI (p = .037). There was a significant effect of the SC intervention on depressive symptoms compared with the UC condition (p = .0169). People in the CCI group also showed mixed results of association with the measures of COPE and emotional expression. The SC condition significantly was associated with higher levels of cancer-related emotional expression, emotional processing, positive reappraisal, and seeking instrumental support. Acceptance, positive reappraisal, self-esteem, cancer-related emotional expression, and expression of positive emotion significantly were related to depressive symptoms.
Neither of the treatments showed a significant impact on cancer-specific distress.
This was a complex study but indicated a clearly positive impact of CCI and SC on depressive symptoms over time when compared to the UC group. A model depicting variables, mediators, and their strengths of association would help to clarify the actions, impacts, and interactions discovered in this study.
Manne, S.L., Rubin, S., Edelson, M., Rosenblum, N., Bergman, Hernandez, E., . . . Winkel, G. (2007). Coping and communication-enhancing intervention versus supportive counseling for women diagnosed with gynecological cancers. Journal of Consulting and Clinical Psychology, 75(4), 615–628.
To compare the efficacy of two psychological interventions to the efficacy of usual care
The coping- and communication-enhancing intervention (CCI) involved challenging assumptions and talking about thoughts and feelings with others. Six hour-long individual sessions were supplemented with a final by-telephone booster session. Session content focused on enhancing coping, educating, and practicing skills; home practice assignments were included. Supportive counseling (SC) involved six hour-long sessions and a by-telephone booster. Rather than topic discussion, SC stressed reactions to cancer, support of existing coping behaviors, and autonomy. Usual care included routine social work consultations. Nineteen experienced therapists provided intervention. Participants were randomly assigned to CCI, SC, or usual care and were assessed preintervention and at three, six, and nine months.
The study included 353 women with primary gynecologic cancer who were in active treatment.
For all patients, symptoms of depression decreased at first. For patients in CCI and SC, symptoms of depression remained relatively flat after six months, but in usual care they began to increase. Authors reported no significant difference between the interventions’ effects and no impact of either intervention on cancer-specific distress.
Manne, S.L., Kissane, D.W., Nelson, C.J., Mulhall, J.P., Winkel, G., & Zaider, T. (2011). Intimacy-enhancing psychological intervention for men diagnosed with prostate cancer and their partners: A pilot study. Journal of Sexual Medicine, 8(4), 1197–1209.
To evaluate (a) the impact of an intimacy-enhancing therapy (IET) versus a usual care (UC) program on survivor and partner psychological outcomes, including distress, well-being, and relationship outcomes (relationship satisfaction and intimacy), (b) the impact of an IET on relationship communication, and (c) the role of preintervention levels of each outcome variable on post-IET intervention outcome variables
Participants received assignment to either an IET or a UC group. The IET intervention consisted of five 90-minute couple sessions delivered by a trained therapist. This person focused on improving couples’ ability to comfortably share their thoughts and feelings to promote mutual understanding and support for cancer concerns and to facilitate emotional intimacy. The IET program techniques evolved from cognitive-behavioral and behavioral marital therapy practice and other published communication skills interventions adapted for prostate cancer. Careful attention was made to ensuring treatment fidelity by videotaping sessions and using manuals to structure the intervention. UC group participants received standard clinic psychosocial care. The IET group received the same surveys following the fifth and final session of the IET (approximately two months post-baseline). The UC and IET participants who did not complete sessions received a second round of surveys eight weeks after baseline assessment.
A pre/post-test pilot design was used.
Seventy-three percent of IET couples attended 80% or more of the sessions, but another 21.6% of the IET group did not attend any sessions following random assignment to the IET group. Treatment fidelity on 114 of 138 sessions averaged 87.4%. Intervention survivors and partners rated the sessions as “quite successful,” but only 72% of the intervention group reported completion of homework assignments as part of the IET program. With study attrition, an intent-to-treat statistical analysis approach was used.
There were no significant treatment effects for general distress, cancer-specific distress, and relationship intimacy for either survivors or partners. There were no significant treatment differences for relationship communication for either survivors or partners. IET effects were largely moderated by baseline couple relationship and psychosocial factors (individual distress). Survivors who had high levels of cancer concerns at baseline significantly reduced those concerns post-IET. Moderating effects of preintervention levels for self-disclosure and perceived partner disclosure and responsiveness resulted from the intervention. The IET program improved cancer-specific distress, low intimacy, martial satisfaction, and communication if a couple experienced problems in these areas before the intervention.
The IET had a marginally significant (p = 0.08) main effect on survivor well-being and improved overall outcomes for couples with fewer personal and relationship resources. Couples with more resources (e.g., higher educational level, stronger marital ties) experienced no improvement from the IET program.
Interventions such as the IET may prove valuable for couples challenged by treatment and outcomes of prostate cancer treatment. As members of the healthcare team, nurses have an obligation to assess prostate cancer survivors about their overall coping skills, learning, and relationship needs to offer patient- and couple-centered interventions to improve the quality of their relationships and adjustment to living with prostate cancer.
Manne, S.L., Ostroff, J.S., Winkel, G., Fox, K., Grana, G., Miller, E., . . . Frazier, T. (2005). Couple-focused group intervention for women with early stage breast cancer. Journal of Consulting and Clinical Psychology, 73, 634–646.
The intervention was a couple-focused support group intervention (90-minute group session over six weeks). The intervention consisted of enhanced support exchanges and coping skills between women with cancer and their partners. One group received the intervention and one group received usual care, which included social work consultations for all women and referral to a psychiatrist or psychologist if indicated. Assessments occurred initially, after the first group session, at the end of group session 6, and at six months for follow-up.
A longitudinal, randomized controlled trial design was used.
Analysis evaluated subgroups of data using growth curves models approach with three-step procedure. For first step, time was considered the only explanatory variable. For second step, demographic, medical, site, treatment, and psychological covariates were examined. Third step examined moderator effects by crossing the intervention group main effect with time and the proposed mean-centered moderators. All multiple mean comparisons were adjusted with Tukey.
Women attending sessions reported significantly less distress and anxiety levels than did women receiving usual care or those who dropped out of the intervention (p = 0.0171). Findings suggest that women who rated their partners as more unsupportive and those who had greater physical impairment had an increased response to the intervention compared to women in the control group. Thirty-five percent dropped out of the intervention. Results via ITT analysis: First step (time) indicated significant decline in anxiety over time ([t344] = -2.21, p = 0.0280) and significant differences among participants both in preintervention anxiety (z = 8.02, p < 0.0001) and in the rates at which anxiety changed over time (z = 2.38, p = 0.0085). Second and third steps steps indicated that interactions involving the intervention group were not significant for anxiety. Effect sizes of intervention were small, ranging from 0.2 to 0.7.
Effect sizes were relatively small (0.2–0.7).