Vondracek, P., Oslejskova, H., Kepak, T., Mazanek, P., Sterba, J., Rysava, M., & Gal, P. (2009). Efficacy of pregabalin in neuropathic pain in paediatric oncological patients. European Journal of Paediatric Neurology, 13, 332–336.
The aim of the study was to evaluate the safety and efficacy of pregabalin in the management of chemotherapy-induced neuropathic pain.
Children were medicated with pregabalin twice daily starting at 75 mg per day and titrated upwards by 75 mg daily with doses ranging from 150–300 mg for eight weeks. No patient was receiving chemotherapy at the time of pregabalin administration. Patients were evaluated prior to treatment and at weeks 2, 4, 6, and 8 of treatment using a visual analog scale. Patients were asked about side effects.
The study was conducted at a single outpatient setting in the Czech Republic.
The study had a prospective trial design.
Visual analog scale
The mean visual analog scale score decreased by 59% from baseline during eight weeks of pregabalin with statistically significant improvement in pain symptoms (p < 0.001). A marked pain relief was noted in 14, moderate pain relief in 10, mild pain relief in two, and no pain relief in two patients. Adverse effects were mild or moderate.
Pregabalin appears to be safe and effective in treating pediatric patients with cancer suffering from chemotherapy-induced peripheral neuropathy. Pregabalin has mild to moderate adverse effects.
Pregabalin has been shown to be effective in relieving pain from chemotherapy in pediatric patients; however, pregabalin is expensive and a controlled drug. Preagabalin has mild to moderate side effects and was tolerated without major complications.
Von Ah, D., Carpenter, J.S., Saykin, A., Monahan, P., Wu, J., Yu, M., . . . Unverzagt, F. (2012). Advanced cognitive training for breast cancer survivors: A randomized controlled trial. Breast Cancer Research and Treatment, 135, 799–809.
To evaluate the efficacy of memory and speed of processing training for improving cognitive function in breast cancer survivors
Patients were randomly assigned to one of three groups: training in speed of processing, memory training, or a wait list control group. The intervention included 10 one-hour sessions of memory and speed of processing training delivered in small groups of three to five patients over six to eight weeks. Specific intervention strategies were adapted from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trials. Follow-up was done at two months.
Patients were in the late effects and survivorship phases of care.
Single-blind, three-group randomized controlled trial
The memory training group demonstrated better immediate (d = 0.59, p = 0.036) and delayed memory performance (d = 0.70, p = 0.013) at the two-month follow-up compared to the control group. Those trained in speed of processing improved immediate memory post-intervention (d = 0.75) and at the two-month follow-up (d = 0.82) (p < 0.01). The memory and speed of processing training groups had significant improvement in perceived cognitive functioning on questionnaires. Compared to controls, speed of processing training was associated with lower symptom distress. Memory training also had a positive effect on anxiety at the two-month follow-up (p = 0.017)
Memory and speed of processing training had significant positive effects on objectively measured and perceived cognitive function among female breast cancer survivors.
Cognitive training as provided here had a significant and at least a moderate positive effect on cognitive function in breast cancer survivors. Cognitive deficits with cancer treatment have substantial negative impacts on quality of life and functioning. Cognitive training is a promising intervention to address these problems.
von Minckwitz, G., Kummel, S., du Bois, A., Eiermann, W., Eidtmann, H., Gerber, B., . . . German Breast Group. (2008). Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study. Annals of Oncology, 19, 292–298.
The purpose of the study was to compare rates of febrile neutropenia between four treatments: (a) ciprofloxacin 500 mg PO BID on days 5–14, (b) G-CSF (filgrastim 5 mg/kg per day or lenograstim 150 mg/m2 per day) on days 5–10, (c) pegfilgratim 6 mg on day 2, and (d) pegfilgrastim plus ciprofloxacin.
A secondary aim was to compare the incidence of neutropenia and other hematologic toxic effects, infection, nonhematologic toxic effects, and hospitalization.
Patients enrolled in the German GeparTrio study from April 2001 and June 2005 who received one of the four neutropenia prophylactic regimens were analyzed. Patients analyzed had completed at least one cycle of TAC and were not randomized to no treatment.
89 outpatient sites in Germany
Active treatment
Retrospective cohort study of women with breast cancer enrolled in the Germany GeparTrio study.
Among the 1,256 patients in the analyses, 1,057 completed all planned cycles of treatment (six cycles, n = 793; eight cycles, n = 264). The combination of pegfilgrastim and ciprofloxacin was statistically significantly better than other regimens for the prevention of overall febrile neutropenia (p < 0.001), febrile neutropenia during the first chemotherapy cycle (p < 0.001), lower incidences of grade 4 neutropenia, prevention of leukopenia and anemia (p < 0.001), fewer hospitalizations (p < 0.001), and for the reduction of stomatitis/mucositis, dysphagia/esophagitis, and diarrhea. Pegfilgrastim alone was as effective as pegfilgrastim and cipro for overall febrile neutropenia (p < 0.001) and for the reduction of grade 4 neutropenia, leukopenia, and anemia (p < 0.01). Daily G-CSF was better than cipro alone for the reduction of grade 4 neutropenia. Thrombocytopenia was lowest for cipro alone (p < 0.001). Infection with neutropenia was not statistically different between groups.
The use of pegfilgratim, especially in combination with ciprofloxacin, is superior to ciprofloxacin alone or daily G-CSF for the reduction of febrile neutropenia, grade 4 neutropenia, and related hospitalizations. No regimen proved superior over others for the prevention of infection with neutropenia.
The administration of daily G-CSF was not given according to protocol of beginning 24 hours after the last dose of chemotherapy with continuation until absolute neutrophil count (ANC) has returned to normal range or for a maximum of 14 days. G-CSF was started at a later time in the cohorts who received G-CSF which could have skewed the results in favor of pegfilgrastim, which was given according to protocol.
The use of pegfilgratim, especially with ciprofloxacin, for the prevention of febrile neutropenia, grade 4 neutropenia, and neutropenic-related hospitalizations appears beneficial for women with stage T2–T4 primary breast cancer. Oncology nurses can advocate for use of this regimen for their patients.
von Gruenigen, V., Frasure, H., Fusco, N., DeBernardo, R., Eldermire, E., Eaton, S., & Waggoner, S. (2010). A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gynecologic oncology patients. Cancer, 116, 4735–4743.
To compare the efficacy of pyridoxine versus placebo for the prevention of hand-foot syndrome (HFS) in patients with recurrent ovarian, metastatic breast, or endometrial cancer who received pegylated liposomal doxorubicin (PLD) chemotherapy. A secondary objective was to compare quality of life (QOL) between patients who experienced HFS during chemotherapy and those who did not.
Patients were randomly assigned to receive pyridoxine 100 mg BID (group A) or placebo (group B). Patients also received standard HFS education and completed a QOL questionnaire. Incidence of HFS was compared between groups.
Patients were undergoing the active treatment phase of care.
This was a randomized, double-blind, placebo-controlled trial.
Pyridoxine as administered in the current study did not prevent HFS in patients who received PLD. No difference existed in the incidence of HFS between patients who received prophylactic pyridoxine and those who received placebo. In addition, the HFS rash appeared to be tolerable in most patients because it did not disrupt patient-rated QOL in this study.
Findings do not support the effectiveness of pyridoxine in the prevention of HFS. The study was likely underpowered. Additional research is needed on strategies to prevent and manage HFS.
von Delius, S., Eckel, F., Wagenpfeil, S., Mayr, M., Stock, K., Kullmann, F., . . . Lersch, C. (2007). Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: Final results of a randomised, controlled, multicenter phase II study. Investigational New Drugs, 25, 173–180.
This study evaluated the efficacy and safety of carbamazepine for the prevention of oxaliplatin-associated neuropathy in patients treated for advanced-stage colorectal cancer.
Patients were randomly assigned to receive carbamazepine 200 mg orally daily, beginning six days before the first oxaliplatin via IV, with dose increases to yield a plasma level of 4-6 mg/dl. All patients received oxaliplatin 85 mg/m² via IV every two weeks, plus folinic acid 500 mg/m² via IV followed by 5-FU 2,000 mg/m² infused over 24 hours every week. A cycle consisted of six weeks of treatment and a two week rest. Groups were compared in relation to worst neurotoxicity and neurotoxicity at each cycle.
The study had a randomized, controlled, multicenter phase II design.
Data were collected at baseline and following each treatment cycle using Levi’s Neurotoxicity Rating Scale (0–4), and peripheral neuropathy score based on sensory symptoms and examination (vibrational sense, strength, and deep tendon reflexes), each scored 0–3.
No group differences were noted in grade of neurotoxicity or in grade 3 or 4 neurotoxicity using the Levi Neurotoxicity Rating Scale for either the worst toxicity across all cycles or cycle-based comparisons. The groups did not differ in scores on the individual components of the peripheral neuropathy score or the overall peripheral neuropathy score based on worst toxicity or cycle-specific comparisons between groups. Of note, only two participants discontinued carbamazepine for CNS side effects.
Because the current study was underpowered, no definitive conclusions can be drawn regarding efficacy and safety.
von Bultzingslowen, I., Brennan, M.T., Spijkervet, F.K., Logan, R., Stringer, A., Raber-Durlacher, J.E., & Keefe, D. (2006). Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis. Supportive Care in Cancer, 14, 519–527.
A systematic review of the English medical literature was performed. Only clinical trials were included in the first search, January 1966–May 2002. In the June 2002–May 2005 review, clinical and preclinical trials were included.
In the 2002 review, 35 studies were identified. In the 2005 review, 14 preclinical and 9 clinical studies were identified. Studies reporting on cytokines or growth factors for the amelioration of chemotherapy- and radiation-induced mucositis throughout the entire alimentary canal were included.
Based on the review, guidelines recommend palifermin at a dose of 60 mg/kg per day for three days prior to conditioning for hematologic malignancies receiving high-dose chemotherapy and total body irradiation (TBI) with autologous stem cell transplantation (SCT). Preliminary results indicated effectiveness for repifermin. Trials are in process for velafermin.
Two randomized studies of granulocyte colony-stimulating factor (G-CSF) showed reduction in mucositis incidence. Two cohort studies demonstrated reduced severity of mucositis. One study did not show any positive results for mucositis. Another showed that use of growth factors was not a significant determinant of oral mucositis. Two studies failed to demonstrate improvement with G-CSF in the radiation setting. Studies demonstrate conflicting results. No recommendation can be made at this time.
One cohort study with granulocyte macrophage colony-stimulating factor (GM-CSF) showed reduction in severity and duration of oral mucositis. Another study showed no effect on radiation-induced oral mucositis. Two studies showed some positive effects for radiation-induced mucositis. Studies demonstrated conflicting results. No recommendation can be made at this time. Two studies with GM-CSF mouthwash demonstrated no positive effects. The Multinational Association of Supportive Care in Cancer guideline has been updated to suggest that GM-CSF mouthwash not be used for the prevention of mucositis in the transplant setting.
For other agents, evidence was insufficient or toxicities too severe to recommend use.
Volovat, C., Bondarenko, I., Gladkov, O., Buchner, A., Lammerich, A., Muller, U., & Bias, P. (2016). Efficacy and safety of lipegfilgrastim compared with placebo in patients with non-small cell lung cancer receiving chemotherapy: Post hoc analysis of elderly versus younger patients. Supportive Care in Cancer, 24, 4913–4920.
To study the potential benefits and risks of using lipegfilgrastim to reduce neutropenia in patients receiving myelosuppressive chemotherapy for advanced non-small cell lung cancer, and to compare the outcomes of older adults (defined as patients aged older than 65 years) and adults
After receiving first-line chemotherapy (cisplatin 80 mg/m2 IV on day 1 and etoposide 120 mg/m2 IV on days 1–3 every three weeks) for non-small cell lung cancer, participants were randomized 2:1 to receive a single subcutaneous injection of lipegfilgrastim 6 mg or placebo, administered approximately 24 hours after the last etoposide infusion. Patients received up to four cycles of cisplatin/etoposide, with the study medication given after each cycle. Monitoring for adverse events continued until three weeks after the last intervention. Blood was drawn (for complete blood count and chemistry testing) before each cycle and on day 15 of each cycle.
PHASE OF CARE: Active antitumor treatment
This study was a post hoc analysis of subgroups of patients who had enrolled in a double-blinded, randomized, controlled trial.
To determine efficacy, the authors studied the incidence of FN following the first cycle of cisplatin/etoposide chemotherapy. FN was defined as an oral temperature greater than 38.5 degrees C on two or more consecutive measurements at least 60 minutes apart, with a concurrent absolute neutrophil count (ANC) less than 0.5 x 109/L, or neutropenic sepsis or potentially life-threatening neutropenic infection. The authors also compared the incidence and duration of severe neutropenia (DSN), defined as grade 4 neutropenia with an ANC less than 0.5 x 109/L; the time to ANC recovery, defined as the time from any post-chemotherapy day with an ANC less than 2 x 109/L to the first day with an ANC of 2 x 109/L or less; and the depth of ANC nadir. For study safety, patients were not assessed for adverse events (AEs) until three weeks after the last dose of study medication.
There was no significant difference in the incidence of FN following the first chemotherapy cycle between the lipegfilgrastim and placebo groups for patients aged 65 years or younger. None of the older patients who received lipegfilgrastim developed FN during the first chemotherapy cycle, compared to 13.3% in the placebo group. The difference in incidence of severe neutropenia between the placebo and lipegfilgrastim groups was more pronounced in younger patients (56.8% versus 27.6%) than in those older than 65 years (66.7% versus 49.1%). In both age groups, the mean DSN during cycle 1 was shorter (0.6 days versus 2.1 days for patients aged 65 years or younger; 1 day versus 3 days in patients aged older than 65 years) for patients who received lipegfilgrastim compared to those who received placebo. Mean time to ANC recovery during cycle 1 was less with lipegfilgrastim than with placebo and was comparable in both age groups (6.8 days versus 13.3 days for patients aged 65 years or younger; 6.5 days versus 12.2 days in patient aged older than 65 years). Similarly, mean depth of ANC nadir during cycle 1 was also higher with lipegfilgrastim than with placebo and was comparable in both age groups (1.6 x 109/L versus 0.7 x 109/L for patients aged 65 years or younger; 1.5 x 109/L versus 0.5 x 109/L for patients aged older than 65 years). Most AEs were likely attributable to the chemotherapy, and the incidence was similar between treatment groups. The exception was the incidence of hypokalemia (6.2% versus 2.1% in patients aged 65 years or younger; 15.1% versus 3.3% in patients aged older than 65 years) and hypophosphatemia (3.6% versus 1.1% in patients aged 65 years or younger; 9.4% versus 3.3% in patients aged older than 65 years), which were higher in the lipegfilgrastim group versus the placebo group. The older adults who received lipegfilgrastim also had a higher incidence of decreased appetite (17%) than the placebo group (6.7%).
In patients aged 65 years and younger, lipegfilgrastim did not decrease the incidence of FN but limited the severity, duration, and time to recovery of neutropenia. In older adults, who have a greater risk for myelosuppression, lipegfilgrastim significantly reduced the incidence of FN in addition to the benefits realized by younger patients.
The addition of lipegfilgrastim to a cisplatin/etoposide chemotherapy regimen for non-small cell lung cancer is beneficial in reducing the incidence, severity, and duration of FN in patients aged older than 65 years. Lipegfilgrastim was generally well tolerated in both the older adult and adult populations, but those aged older than 65 years may be at risk for hypokalemia, hypophosphatemia, and decreased appetite. The sample sizes in this study were too small to be of value.
Vokurka, S., Bystricka, E., Scudlova, J., Mazur, E., Visokaiova, M., Vasilieva, E., …Streinerova, K. (2011). The risk factors for oral mucositis and the effect of cryotherapy in patients after the BEAM and HD-l-PAM 200 mg/m2 autologous hematopoietic stem cell transplantation. European Journal of Oncology Nursing, 15, 508–512.
To evaluate the characteristics of oral mucositis in autologous hematopoietic stem cell transplantation (HSCT) after HD-L-PAM (high-dose [HD] methotrexate plus vincristine, HD-doxorubicin, cisplatin, and HD-melphalan) 200 mg/m2 and BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) conditioning regimens and to analyze the impact of simple and basic clinical and laboratory factors on oral mucositis incidence
Patients who were admitted to a transplant hospital to receive BEAM or HD-L-PAM 200 mg/m2 chemotherapy followed by autologous HSCT were recruited to the study. To be included, patients had to have healthy oral mucosa without symptoms of inflammation or local infection at baseline and signed informed consent. Patients were excluded from the study if they had a history of head or neck or total body radiotherapy, received keratinocyte growth factors or amifostine for oral mucositis prophylaxis, or participated in any other trial comparing any new drugs for oral mucositis prophylaxis or treatment.
Oral cavity monitoring began on the first day of admission and continued throughout the inpatient stay. Beginning on the first day of chemotherapy administration, patients used mouthwash after main meals, before sleep, and as desired. Patients could use their mouthwash of choice, selecting from chlorhexidine, salvia officinalis, providone-iodine, normal saline, Listerine®, benzydamine, or water. Patients were instructed to gargle for two minutes with the solution of choice. Patients were instructed to use soft toothbrushes. Cryotherapy with lollipops, ice-cold water, or crushed ice was added to the protocol in 2008.
Basic clinical and laboratory data representing individual variables, tested as oral mucositis risk factors, were recorded. Basic statistical univariate analyses were performed using statistical software with Mann-Whitney. The p values comparing the presence and absence of the characteristics and p values < 0.05 were considered indicative of statistically significant differences in relation to mucositis occurrence.
This was a multisite study conducted in the inpatient setting at the University Hospital in Pilsen, Czech Republic; University Hospital in Olomouc, Czech Republic; University Hospital in Kosice, Slovak Republic; Silesian Medical Academy in Katowice, Poland; and Pavlov Medical University in St. Petersburg, Russia.
This was a multicenter, prospective, observational evaluation with oral cavity care.
This observational study verified the potential efficacy and feasibility of oral cryotherapy in melphalan short-infusion administration with HD-L-PAM and multidrug BEAM conditioning regimens. Much larger and more homogenous cohorts of patients are needed for future research on the oral mucositis risk factors.
The study findings are limited because of the lack of random assignment, blinding, and an appropriate control group.
Based on the results of this observational trial, the nonprovision of oral cryotherapy is a risk for the development of oral mucositis in patients after autologous HSCT with BEAM or HD-L-PAM conditioning regimens. Maximum effort should be targeted toward the education of medical and nursing teams to implement cryotherapy as a standard prophylactic approach in melphalan regimens.
Vokurka, S., Bystricka, E., Koza, V., Scudlova, J., Pavlicova, V., Valentova, D., et al. (2005). The comparative effects of povidone-iodine and normal saline mouthwashes on oral mucositis in patients after high-dose chemotherapy and APBSCT: Results of a randomized multicentre study. Supportive Care in Cancer, 13(7), 554–558.
The goal of the study was to define the role of anti-microbial solutions.
Two groups of patients were compared: Normal saline mw povidone-iodine mw.
Group A used NS for oral rinsing and Group B use povidone-iodine diluted 1:100 water. The solutions were blinded to patients. Study nurse started first day and covered the whole inpatient stay. It was a 2 min gargle 4x/day IN the presence of OM the mouthwashes could be more frequent according to patients' wishes. Used soft toothbrush 4 x/day. If bleeding occurred would do only MW
Mouthwash was blinded.
The study was comprised of 132 patients. Patients were treated with hi-dose BEAM or HD-LPAM followed by APSCT.
Study group A had 65 pts or group B had 67 patients, NS or povidone iodine.
Multicenter
Jan 2002- June 2004
Prospective, randomized
No significant difference with oral mucositis (p = 1.0) characteristics in both groups and fever of unknown origin (p = 1.0) and other infections (p = 0.34). Povidone-iodine was less tolerable.
No healing effect with betadine.
OM occurred more significantly in females than in males (p = .0016) and was worse and of longer duration.
Patients disliked the taste of povidone-iodine, less use of povidone-iodine.
Note appropriate dose of povidone-iodine.
Vokurka, S., Skardova, J., Hruskova, R., Kabatova-Maxova, K., Svoboda, T., Bystricka, E., et al. (2011). The effect of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) on oral microbial colonization and pain control compared with other rinsing solutions in patients with oral mucositis after allogeneic stem cells transplantation. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 17(10), CR572-6.
To assess the efficacy, tolerance, and impact on oral cavity microbial colonization in patients with OM post-allogeneic hematopoietic stem cell transplantation.
Oral cavity nursing care with benzydamine, chlorhexadine, or saliva solutions was started on the first day of conditioning chemotherapy administration and covered the entire inpatient stay. Gelclair was begun for 22 consecutive patients on the day of the development of OM and continued until the OM resolved when oral cavity nursing care was resumed until the patient was discharged.
The study was comprised of 37 patients, age 19-68 years.
There were 51 males and 49 females.
KEY DISEASE CHARACTERISTICS: AML, ALL, CLL, CML, HL, NHL, MDS, MM
SITE: Single site
LOCATION: Stem Cell Transplant Center of Hokkaido University Hospital
PHASE OF CARE: Active treatment
Prospective observational study in adults with oral mucositis post-allogeneic stem cell transplant in 2008-2009.
There was no difference in the median value of tolerability of the rinses. There was also no difference in the improvement of oral intake. The duration of pain relief was significantly longer in the Gelclair group, and significantly fewer pathogens were found in the Gelclair group compared to the control group. There was significant increase in pathogen colonization after discontinuation of the Gelclair in the post OM phase.
Gelclair may be helpful in the management of OM and pain in some patients after allogeneic stem cell transplant. Use of Gelclair seemed to have helped protect the mucosa from enterococcus and candida colonization.
Small sample <30
No cost comparison performed.
Further randomized controlled studies are needed to assess the efficacy of Gelclair in the transplant population. There is also further study needed regarding the reduction in incidence of pathogen colonization with the use of Gelclair and to clarify the cost effectiveness of this treatment regimen.