Predictors of the usefulness of duloxetine for chemotherapy-induced peripheral neuropathy

Duloxetine is an effective therapeutic agent for chemotherapy-induced peripheral neuropathy (CIPN). However, predictors of duloxetine response have not been adequately explored. Therefore, this retrospective study was performed to identify predictive factors of duloxetine response in CIPN patients to guide future strategies to improve the quality of life of patients undergoing chemotherapy. The participants were 74 cancer patients who were given duloxetine for relief of CIPN at our institute between October 2010 and January 2016. Variables were extracted from clinical records for regression analysis of factors related to relief of CIPN. We evaluated the effect of duloxetine 2 weeks after administration. Groups were categorized according to degree of improvement: poor, effective, and very effective. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the usefulness of duloxetine. Threshold measures were examined using a receiver operating characteristic analysis (ROC) curve. Body height [odds ratio (OR) 0.943, 95% confidence interval (CI) 0.889–0.997; P = 0.0387], history of docetaxel use (OR 0.084, 95% Cl 0.009–0.814; P = 0.0325), and site of symptom (upper limb) (OR 3.848, 95% Cl 1.072–13.807; P = 0.0387) were significant factors related to the effect of duloxetine. ROC curve analysis of the poor effect group indicated a threshold for body height of >171.4 cm (area under the curve [AUC] = 0.61). In conclusion, body height (low), history of docetaxel use (less), and site of symptom (upper limb) were shown to be predictive factors for the usefulness of duloxetine for CIPN in patients undergoing chemotherapy.     

Use of an alpha lipoic,methylsulfonylmethane and bromelain dietary supplement (Opera<Superscript>®</Superscript>) for chemotherapy-induced peripheral neuropathy management,a prospective study

Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA^® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA^® supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents. Patients were enrolled at the first clinical manifestation of neuropathy. CIPN was assessed at the enrollment visit and subsequently repeated every 3 weeks until 12 weeks. Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA^®. Analysis of VAS data showed reduction in pain perceived by patients. According to NCI-CTC sensor and motor score, mISS scale and TNSc scale, both pain and both sensor and motor neuropathic impairment decreased after 12 weeks of treatments. Treatment with OPERA supplement was well tolerated; no increase in the toxicity profile of any of the therapeutic regimen that the patients were undergoing was reported. OPERA^® was able to improve CIPN symptoms in a prospective series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. Prospective RCT in a selected patients’ population is warranted to confirm its promising activity.     

Comparison of toxicity profile and tolerability between two standard of care paclitaxel-based adjuvant chemotherapy regimens in breast cancer

In breast cancer, there are two widely used paclitaxel-based adjuvant chemotherapies, either dose dense paclitaxel (ddP) or weekly paclitaxel (wP). To our knowledge, the comparisons of toxicity and tolerability between the two regimens have never been reported in the literature. This is a retrospective single-institution charts review of breast cancer patients who were treated with paclitaxel-based chemotherapy either ddP or wP. In total, 76 and 45 patients with breast cancer received adjuvant standard ddP and wP, respectively. Patient characteristics in both groups were comparable. Our results showed no statistical significant difference in toxicity profile and tolerability between the two regimens. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) was equally observed in both schedules. Furthermore, grade 3 and 4 CIPN was observed in 17 and 18 %, respectively (p = 0.93). In terms of tolerability, both regimens resulted in similar rates of hospitalization and treatment discontinuation. Our data analysis indicates no significant difference in toxicity profile between the two standard paclitaxel regimens in breast cancer. However, this is a small sample-sized retrospective study and further prospective trial with a larger sample size is warranted.     

Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver

Background

Liver metastases in patients with cancer are associated with poor survival. We hypothesized that hepatic arterial infusion (HAI) of oxaliplatin combination therapy would have antitumor activity in these patients.

Patients and methods

Patients with advanced cancer and predominant liver metastases were treated on a phase I study of HAI oxaliplatin in combination with systemic bevacizumab, with or without HAI or systemic fluorouracil and/or leucovorin and/or cetuximab. Patients were divided into two treatment arms according to KRAS mutational status and physician choice. A “3 + 3” design was used.

Results

Among 76 patients (median age 61 years; 34 women; median number of prior therapies 4), the most common cancer was colorectal (CRC) (n = 58). Overall, the only dose-limiting toxicity was Grade 3 diarrhea (n = 2). The most common treatment-related toxicities were hypertension (n = 40), nausea (n = 29), fatigue (n = 28), and transaminitis (n = 26). Of 76 patients, one (1 %) had a complete response (CR), 12 (16 %) had a partial response (PR), and 12 (16 %) had SD for ≥6 months (total CR/PR/SD ≥6 months 25/76 = 33 %). In CRC (n = 58), total CR/PR/SD ≥6 months was 31 % (n = 18). Both patients with pancreatic neuroendocrine tumors achieved a PR (24+ months) and a CR (6+ months). Time to treatment failure (TTF) on the current regimen was 3.5 versus 2.8 months on patients’ prior systemic treatment (p = 0.37).

Conclusions

HAI oxaliplatin combination therapy with 5-fluorouracil, leucovorin, bevacizumab, and/or cetuximab was well tolerated and had antitumor activity in selected heavily pretreated patients with predominant liver disease.     

Effectiveness and safety of cabazitaxel plus prednisolone chemotherapy for metastatic castration-resistant prostatic carcinoma: data on Korean patients obtained by the cabazitaxel compassionate-use program

Purpose

To report the efficacy and safety of using cabazitaxel plus prednisolone chemotherapy to treat Korean patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel therapy.

Methods

This cohort study enrolled 26 mCRPC patients. Treatment consisted of 25 mg/m² cabazitaxel that was intravenously administered every 3 weeks, in addition to twice-daily 5 mg prednisolone.

Results

The median patient age was 67 years (range = 53–82), median Eastern Cooperative Oncology Group performance status was 1 (range = 0–2), Gleason score was ≥8 in 25 patients (96 %), and median serum prostate-specific antigen (PSA) was 95.3 ng/mL (interquartile range = 9.1–297.7). A total of 180 treatment cycles were administered, and a median of five cycles were administered per patient (range = 1–23). A PSA response was observed in 32 % of evaluable patients. Tumor response was evaluated in eight patients, and three and four patients achieved partial response and stable disease, respectively. Over a median follow-up duration of 23.4 months (95 % CI 11.1–35.6), median time to treatment failure was 4.2 months (95 % CI 1.8–6.6) and median time to progression was 8.5 months (95 % CI 3.0–13.1). Median overall survival was 16.5 months (95 % CI 12.1–20.9). Grade 3 or worse febrile neutropenia developed in eight patients (31 %) and neutropenic infection in four patients (15 %).

Conclusion

Cabazitaxel plus prednisolone chemotherapy can be used to treat Korean mCRPC patients. Prophylactic growth factor support should be considered for patients at high risk of neutropenic fever or infection.     

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical–pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel.     

Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy

Peripheral neuropathy induced by cancer chemotherapy represents a large unmet need for patients due to the absence of treatment that can prevent or mitigate this common clinical problem. Chemotherapy-induced peripheral neuropathy (CIPN) diagnosis and management is further compounded by the lack of reliable and standardized means to diagnose and monitor patients who are at risk for, or who are symptomatic from, this complication of treatment. The pathogenesis and pathophysiology of CIPN are not fully elucidated, but there is increasing evidence of damage or interference with tubulin function. The diagnosis of CIPN may present a diagnostic dilemma due to the large number of potential toxic etiologies and conditions, which may mimic some of the clinical features; the diagnosis must be approached with care in such patients. The incidence and severity of CIPN is commonly under-reported by physicians as compared with patients. The development of new and reliable methods for the assessment of CIPN as well as safe and effective treatments to prevent this complication of treatment would represent important medical advancements for cancer patients.     

Effective Treatment of Acute Otitis Externa: a Comparison of Steroid Antibiotic Versus 10% Ichthammol Glycerine Pack

To compare the efficacy of treatment between steroid–antibiotic and 10% Ichthammol glycerine packs (IG packs) in acute otitis externa. A prospective, randomized clinical trial between steroid–antibiotic and 10% IG pack which was performed in department of ENT-HNS, Kathmandu University Hospital, Dhulikhel from July 2009 to December 2009 on 82 patients. Pain was assessed by Numerical Rating Scale (NRS) and edema was assessed by dividing the external auditory canal in four quadrant giving score of 25% for each on the day of presentation and subsequent visits till tragal tenderness and edema subsided. Age group among studied patients ranged from 10 to 60 years, with mean of 23.5 years. Out of which 42 (51.2%) were females and 40 (48.8%) were males. Average number of visits in 10% IG pack group (n = 41) was 5.4 days (2–5 visits) while in steroid–antibiotic group (n = 41) it was 3.5 days (2–5 visits). There was statistically significant decrease in the number of visits in steroid group (P < 0.05). Similarly, decrease in pain score in second visit was statistically significant (P = 0.02) in steroid–antibiotic group as compared to 10% IG pack, while the edema score in second visit while comparing steroid–antibiotic group with 10% IG pack was statistically not significant (P = 0.07), whereas it was statistically highly significant on fourth visit (P = 0.001). Since the control of pain and edema is more and hence the number of visits is significantly less in steroid–antibiotic packing group, so it is worthwhile to use steroid–antibiotic pack for effective treatment of acute otitis externa.     

Preoperative prediction of the size of pure ductal carcinoma in situ using three imaging modalities as compared to histopathological size: does magnetic resonance imaging add value?

Purpose

The purpose of this study was to evaluate whether magnetic resonance imaging (MRI) and ultrasonography add value to traditional mammography in an Asian population with ductal carcinoma in situ (DCIS).

Methods

Data of 244 patients with pure DCIS treated at Severance Hospital between 2013 and 2015 were analyzed retrospectively. Data extracted included age, preoperative diagnosis, tumor size on preoperative imaging studies, and final histopathological tumor type and size, including hormone receptor status. The extent of correlation between imaging and histopathological tumor sizes was evaluated using a variety of methods, including Bland–Altman analysis.

Results

The mean patient age was 52.39 years (SD = 10.31). The mean measurements of the tumor on preoperative ultrasonography, mammography, MRI, and histopathology were 1.80 (SD = 1.23) cm, 2.97 (SD = 1.92) cm, 2.53(SD = 1.84) cm, and 1.88 (SD = 1.36) cm, respectively. The mean differences in tumor size between ultrasonography, mammography, and MRI compared with histopathology were ?0.09 (SD = 1.39), 1.09 (SD = 1.89), and 0.65 (SD = 1.78), respectively. The correlation between the sizes was significant with r values for ultrasonography, mammography, and MRI of 0.447 (SE = 0.061), 0.375 (SE = 0.042), and 0.409 (SE = 0.043), respectively. Mammography and MRI estimated tumor size significantly better for patients older than 50 years (p = 0.045 and <0.001, respectively). Mammography also provided good estimation for patients with a body mass index under 25 (p = 0.041).

Conclusion

MRI is better at estimation of histopathological DCIS size compared with mammography. However, ultrasonography had better estimation compared with MRI and mammography, probably owing to the high breast density in this population.

     

RC0639: phase II study of paclitaxel, trastuzumab, and lapatinib as adjuvant therapy for early stage HER2-positive breast cancer

Lapatinib adds to the efficacy of trastuzumab in preclinical models and also in the neo-adjuvant setting. This study assesses the safety and feasibility of adding lapatinib to paclitaxel and trastuzumab (THL) as part of the adjuvant therapy for HER2-positive breast cancer (HER2+ BC). In this single-arm phase II study, patients with stages I–III HER2+ BC received standard anthracycline-based chemotherapy followed by weekly taxane, with concurrent standard trastuzumab, plus daily lapatinib for a total of 12 months. The primary endpoint was symptomatic congestive heart failure, secondary endpoints included overall safety. A total of 109 eligible patients were enrolled. Median follow-up is 4.3 years. No patients experienced congestive heart failure while on treatment. Mean left ventricular ejection fraction at baseline and at the end of THL were 63.6 % (N = 109, SD = 5.7) and 59.8 % (N = 98, SD = 8.1), respectively [mean change ?3.95 % (N = 98, SD = 8.3), p < 0.001]. One hundred and two patients initiated post-AC treatment; of them, 31 % experienced grade 3 (no G4) diarrhea with lapatinib at 750 mg/day. The addition of lapatinib to paclitaxel and trastuzumab following AC does not add cardiac toxicity. Lapatinib dose of 750 mg/day in combination with standard chemotherapy plus trastuzumab has acceptable overall tolerability.     

Functional Endoscopic Sinus Surgery Versus Balloon Sinuplasty with Ethmoidectomy: A 2-year Analysis in Pediatric Chronic Rhinosinusitis

To evaluate the 2-year post-operative outcomes of pediatric patients with chronic rhinosinusitis (CRS) treated with balloon catheter sinuplasty (BCS) and ethmoidectomy compared to functional endoscopic sinus surgery (FESS). Two-group, retrospective cohort study of 28 children with CRS was performed. Of these 28 participants, 15 were treated with traditional FESS (53.6 %) and 13 (46.4 %) underwent traditional ethmoidectomy with balloon sinuplasty. Pre-operative and 2-year postoperative total symptom scores and medications were compared. To examine the potential long-term differences in surgical outcomes and surgical procedure on symptom outcome, one-tailed Chi square analyses were employed. The mean age of the children examined was 9.3 (SD = SD = 4.1; range 3–18) and 61.9 % were male. Pre-operative symptomatology, medication and Lund Mackay scores were evaluated for both groups and no significant differences were identified. Overall, 73.3 % of children that underwent traditional FESS and 76.9 % of those who had BCS with ethmoidectomy reported significant long-term improvement in at least one of their pre-operative sinus complaints. Our data suggests that both BCS with ethmoidectomy and traditional FESS are effective treatment options for uncomplicated CRS and result in long-term alleviation of core sinus complaints, as well as decreased sinus related medication use. Larger prospective studies are needed to further evaluate these procedures.     

Using wearables to screen motor performance deterioration because of cancer and chemotherapy-induced peripheral neuropathy (CIPN) in adults - Toward an early diagnosis of CIPN

ObjectiveAn essential component for optimizing quality of life in adults with cancer is determining the degree to which therapy may negatively impact motor-performance, so that patients can maintain their quality of life and independence. This study examined whether instrumented gait and balance could determine the magnitude of deterioration in motor-performance from chemotherapy-induced peripheral neuropathy (CIPN).MethodsWe recruited 84 adults with cancer (age = 71.1 ± 9.7 years old, BMI = 26.8 ± 6.2 kg/m², gender = 56%female) and 57 age-matched non-cancer patients (age = 69.5 ± 9.8 years old, BMI = 27.1 ± 6.0 kg/m², gender = 79%female). Based on clinical screening, the group with cancer was classified into two groups: participants with CIPN (CIPN+) and without CIPN (CIPN-). Gait and balance were quantified using validated wearables. The Vibration Perception Threshold (VPT) test was used to stratify the CIPN+ group into mild (Mild-CIPN) and severe (Severe-CIPN) subgroups.ResultsAll gait and balance parameters were deteriorated in the group with cancer compared to non-cancer group with the largest effects observed for stride-time (11%, Cohen's effect size d = 1.00, p < 0.001) and eyes-closed ankle sway (94%, d = 0.49, p = 0.001). The same trend was observed when the Severe-CIPN subgroup was compared to the Mild-CIPN. VPT correlates significantly with motor deterioration, with the largest correlation found in stride-time (Rho = 0.37, p = 0.007). Severe-CIPN subjects were significantly older and overall had more deterioration in the majority of motor-performance parameters after adjusting for age (p < 0.050).ConclusionThese results confirmed the negative impact of CIPN on motor-performance with the largest effects on ankle stability and stride-time. VPT is a predictor of motor deterioration and may be used to determine the severity of CIPN symptom.     

Subclinical pretreatment sensory deficits appear to predict the development of pain and numbness in patients with multiple myeloma undergoing chemotherapy

Purpose

Chemotherapy-induced peripheral neuropathy is a major complication in the treatment for cancer, including multiple myeloma (MM). Patients may develop painful and non-painful (e.g., numbness) neuropathy symptoms that impair function and often persist after therapy is terminated. This study tested the hypothesis that baseline subclinical neuropathy, as assessed by sensory thresholds, is related to the development of neuropathy symptoms (e.g., pain and numbness) in patients with MM undergoing treatment with chemotherapy.

Methods

Patients (n = 56) who had undergone two or fewer cycles of induction therapy and who had no evident neuropathy were assessed using quantitative sensory tests to determine multiple-modality sensory thresholds. Patient-reported pain and numbness were assessed through induction therapy (16 weeks) via the MD Anderson Symptom Inventory. A subset of participants (n = 15) continued reporting on their symptoms for an additional 16 weeks (“maintenance phase”).

Results

Patients with sharpness detection deficits at baseline (n = 11, 20 % of sample) reported less severe pain and numbness during induction therapy and less numbness during maintenance therapy (P < 0.05). During the maintenance phase, patients with warmth detection deficits (n = 5, 38 % of sample) reported more severe pain and numbness, and those with skin temperature deficits (n = 7, 47 % of maintenance sample) reported more severe pain (P < 0.05). These deficits were related to patient reported difficulty walking, a common symptom of peripheral neuropathy.

Conclusion

Our results suggest that baseline subclinical sensory deficits may be related to a patient’s risk for developing chemotherapy-induced peripheral neuropathy.     

Suicide ideation in pediatric and adult survivors of childhood brain tumors

Survivors of pediatric brain tumors are at risk for long-term psychological morbidities. The current study investigated the prevalence and predictors of suicide ideation (SI) in a clinical sample of youth and adult survivors. Retrospective chart reviews were completed for 319 survivors of pediatric brain tumors who were assessed via clinical interview during routine neuro-oncology clinic visits between 2003 and 2007. Survivors were, on average, 18.0 years of age (SD = 4.9) and 10 years from diagnosis (SD = 5.0) at their most recent follow-up. The most common diagnosis was low-grade glioma (n = 162) followed by embryonal tumors (PNET/medulloblastoma; n = 64). Multivariable logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for SI. Nearly 12 % of survivors (11.7 %, n = 37) reported SI. Five survivors (1.5 %) had documented suicide attempts, though none were fatal. In a multivariable model, adjusting for sex and age, history of depression (OR = 20.6, 95 % CI = 4.2–101.1), psychoactive medication treatment (OR = 4.5, 95 % CI = 1.8–11.2), observation or surgery only treatment (OR = 3.7, 95 % CI = 1.5–9.1), and seizures (OR = 3.6, 95 % CI = 1.1–11.1) were significantly associated with SI in survivors. Survivors of pediatric brain tumors appear to be at risk for experiencing SI. Our results underscore the importance of a multidisciplinary approach to providing follow-up care for childhood brain tumor survivors, including routine psychological screenings.     

Clinical and genetic predictors of paclitaxel neurotoxicity based on patient- versus clinician-reported incidence and severity of neurotoxicity in the ICON7 trial

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel, with no reliable method to identify at-risk patients. We investigated the incidence and risk factors including genetic polymorphisms associated with the development of CIPN based on clinician and patient reporting of neuropathic symptoms.Patients and methodsRisk factors for the development of CIPN were examined in 454 patients treated with paclitaxel/carboplatin from the International Collaboration on Ovarian Neoplasms 7 (ICON7) trial. Neuropathy was graded by clinicians by standard adverse event reporting and by patients utilising OV28 questionnaire. Genetic risk factors were examined by selecting six single nucleotide polymorphisms in genes associated with microtubule function. Risk factors were assessed via dose-to-event cox regression models.ResultsGrade >2 neuropathy was reported by clinicians in 28% of patients, while 67% of patients reported ‘quite a bit’ or ‘very much’ tingling or numbness. Agreement between clinicians and patients was poor (κ = 0.236, 95% confidence interval, 0.177–0.296, P < 0.001). Older age, bevacizumab treatment and bowel resection were associated with clinician reported CIPN, while older age and volume of residual disease were associated with patient-reported neuropathy. There were no significant associations between clinician-reported neuropathy or patient-reported neuropathy and TUBB2, CEP72 or individual MAPT or GSK3B SNPs, however MAPT additive polymorphisms were associated with patient-reported neuropathy and GSK3B additive polymorphisms were associated with clinician reported CIPN.ConclusionsThere was significant discordance between patient- and clinician-reported neurotoxicity. The lack of consensus regarding optimal outcome measures and whose opinion with regard to CIPN takes precedence is a limitation in the investigation of risk factors for CIPN. Care must be taken to select and include patient-reported outcome measures in CIPN assessment to enable accurate identification of genetic and other risk factors for neuropathy.     

Quantitative assessment of chemotherapy‐induced peripheral neurotoxicity using a point‐of‐care nerve conduction device

Chemotherapy‐induced peripheral neurotoxicity (CIPN) seriously impairs patients’ quality of life cumulatively and dose‐dependently. Because assessment of CIPN usually depends on patients’ subjective evaluation of symptoms, objective and quantitative measures are needed. We evaluated a point‐of‐care nerve conduction device (POCD), previously validated for the assessment of diabetic peripheral neuropathy. Sensory nerve action potential (SNAP) amplitude and sensory nerve conduction velocity (SNCV) of the sural nerve were measured using a portable, automated POCD (DPNCheck; NeuroMetrix Inc., Waltham, MA, USA) in patients with a clinical diagnosis of CIPN of grade 1 or higher. We compared SNAP and SNCV among patients with different grades of CIPN according to the Common Terminology Criteria for Adverse Events. A total of 50 patients (22 men, 28 women; median age, 64 years; grade 1/2/3, 21/18/11) were evaluated. Anticancer drugs responsible for CIPN were cisplatin in five patients, oxaliplatin in 15, carboplatin in 5, paclitaxel in 16, docetaxel in 14, nab‐paclitaxel in 7, vincristine in 6, and bortezomib in 3. Unadjusted SNAP was 8.45 ± 3.67 μV (mean ± SD) in patients with grade 1 CIPN, 5.42 ± 2.68 μV with grade 2, and 2.45 ± 1.52 μV with grade 3. Unadjusted SNCV was 49.71 ± 4.77 m/s in patients with grade 1 CIPN, 48.78 ± 6.33 m/s with grade 2, and 44.14 ± 7.31 m/s with grade 3. The adjusted SNAP after controlling for age significantly differed between each CTCAE grade (P < 0.001, ancova ). The adjusted SNCV after controlling for age and height also differed significantly (P = 0.027). Differences in the severity of CIPN could be detected objectively and quantitatively using this POCD.     

Effect of Exercise on Taxane Chemotherapy–Induced Peripheral Neuropathy in Women With Breast Cancer: A Randomized Controlled Trial

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse effect of taxanes. We sought to evaluate the effect of exercise on taxane CIPN in women with breast cancer.Patients and MethodsWomen (n = 27) were randomized to immediate exercise (IE, during taxane chemotherapy) or delayed exercise (DE, after chemotherapy). Supervised aerobic, resistance, and balance training was offered 3 days a week for 8-12 weeks. CIPN symptoms and quality of life were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and CIPN20 (scored from 0 to 100). The percentage of participants reporting moderate to severe sensory symptoms (‘3/4’ or ‘4/4’ for CIPN20 sensory items) was also evaluated, along with clinical sensory testing at the lower limb (vibration sense and pinprick). Taxane treatment adherence, including relative dose intensity, was extracted from patient medical records. Assessments occurred at: baseline (before taxane chemotherapy), pre-cycle 4 (before the final taxane cycle), the end of chemotherapy, and follow-up (10-15 weeks after chemotherapy).ResultsNo differences in the EORTC QLQ CIPN20 symptom scores were detected between groups at any time point. At pre-cycle 4, there was a significant difference between groups in patient-reported moderate to severe numbness in the toes or feet (IE: n = 1, 9%, DE: n = 7, 50%, P = .04) and impaired vibration sense in the feet (IE: n = 2, 18%, DE: n = 10, 83%, P < .01). Overall global health status/quality of life was higher in IE compared to DE at the end of chemotherapy (P = .05), yet both groups had worse CIPN20 sensory (Δ24.3 ± 4.6, P < .01) and motor symptom scores (Δ10.5 ± 1.9, P < .01) relative to baseline. By the end of chemotherapy, no differences between groups were found for moderate to severe numbness in the toes or feet (P = 1.0) or impaired vibration sense in the feet (P = .71). More IE participants received ≥ 85% relative dose intensity (IE: n = 12, 100%, DE: n = 10, 67%, P < .05).ConclusionExercise may attenuate CIPN over the course of taxane chemotherapy and possibly improve taxane adherence in women with breast cancer. These findings, as well as whether exercise can attenuate CIPN by the end of taxane chemotherapy, should be confirmed in larger trials.     

Vaginal and sexual health treatment strategies within a female sexual medicine program for cancer patients and survivors

Purpose

We sought to evaluate patient adherence and response to simple vaginal and sexual health treatment strategies in female cancer patients receiving treatment at a female sexual medicine and health program and identify improvements of physical symptoms, per patient and clinical evaluation.

Methods

Evaluability criteria included gynecologic exam at initial visit, at least one follow-up with gynecologic exam within 8 months of initial visit, and all consecutive follow-ups <6 months apart. Demographics, medical information, and clinical assessments from 175 evaluable patients with at least one follow-up from 09/12 to 10/14 were analyzed. The majority of patients were being treated for or had a history of breast (n = 90, 53 %), gynecologic (n = 54, 32 %), or colorectal/anal (n = 15, 9 %) cancers. An assessment form included a clinician evaluation, Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), and patient-reported outcomes. Compliance with treatment recommendations were summarized, and changes over time were compared for clinical outcomes.

Results

Mean number of visits was 3.43. Mean age was 55.4 years; 92 % (n = 155/169) were in menopause. Treatment strategies included rationale and instruction for use of vaginal moisturizers, lubricants, pelvic floor exercises, and dilator therapy, in addition to psychosexual education regarding sexual changes (response, anatomy, and function) associated with cancer treatment and support. At last assessment, 89 % had complied with the clinical recommendation (moisturize 2–5+ times/week). Vaginal pH scores >6.5 declined over time (p = 0.03). VAS scores improved by last assessment (p < 0.001), as did VuAS scores (p = 0.001). Sexual function scores significantly improved (p < 0.001), confidence about future sexual activity increased (p = 0.004), and sexual/vaginal health concerns decreased (p = 0.00003).

Conclusion

Significant changes were observed in women using treatment strategies, with improvement in vulvovaginal symptoms, a decrease in elevated vaginal pH and pain with exams, enhanced sexual function, and increased intimacy confidence.

Implications for Cancer Survivors

These findings have high clinical relevance for symptom management with improvement of sexual function using simple strategies and clinical tools in the oncology setting.

     

Pediatric chemotherapy induced peripheral neuropathy: A systematic review of current knowledge

BackgroundThe dramatic increase in the number of childhood cancer survivors over the last 60 years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches.MethodsNeurotoxicity data was systematically collated from Medline, Embase and Pubmed and analysed for quality, relevance and originality in three stages prior to inclusion. Quality scoring was done using the QUALSYST assessment tool.ResultsA total of 61 studies met inclusion criteria. Peripheral neuropathy is common and may be long lasting with characteristics specific to each chemotherapy agent. There is significant variability in reported incidence and natural history, related to challenges in clinical assessment and diagnosis. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication and patient factors such as age and inherited susceptibilities. Recent identification of individual genetic variations has advanced understanding of pathomechanisms and may direct future treatment approaches.ConclusionWhile these studies guide suggestions for current clinical practice, further systematic research with development of strategies for amelioration and prevention of CIPN is necessary. Standardised assessment protocols and objective outcomes measures of CIPN applicable to patients of different ages are critical to enabling the development of novel treatments and facilitation of future clinical trials and treatment individualisation.     

Treatment strategies for chemotherapy-induced peripheral neuropathy: potential role of exercise

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting effect of cancer therapy that often has negative implications on a patient’s quality of life. The pain associated with CIPN has long been recognized as one of the most difficult types of pain to treat. Historically, much effort has been made to explore pharmacological therapies aimed at reducing symptoms of CIPN. While many of these agents provide a modest relief in the symptoms of peripheral neuropathy, many have been shown to have additional negative side effects for cancer patients. Therefore, the authors suggest exercise rehabilitation as one lifestyle modification that may positively impact the lives of patients with CIPN. To our knowledge, there are currently no published clinical trials examining the role of exercise in preserving neurological function following chemotherapy. However, investigations using low-to-moderate intensity exercise as an intervention in patients with diabetic peripheral neuropathy and hereditary motor and sensory neuropathies have produced promising results. Given that cancer patients appear to tolerate exercise, it seems plausible that exercise rehabilitation could be used as an effective strategy to minimize CIPN-induced detriments to quality of life.