Prospective observational study of chemotherapy-induced alopecia after sequential FEC + taxane and the effects of age in breast cancer patients.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a common and quite distressing adverse effects of chemotherapy. There are few detailed observational studies of CIA or of the impact of age on CIA. We performed a prospective observational study to investigate the prevalence and degree of CIA, including CIA of eyebrows, eyelashes, and body, and we examined patient's recovery from CIA, focusing on age-depending effects. METHODS: We analyzed 68 female Japanese patients with breast cancer (median age 53 years, range 29-76 years) who received perioperative adjuvant chemotherapy with fluorouracil/epirubicin/cyclophosphamide (FEC) and taxane. A questionnaire was administered at the point of chemotherapy completion and 6 and 12 months after chemotherapy completion. RESULTS: CIA occurred in all patients, with severe hair loss irrespective of age. CIA occurred mainly in the scalp but also in the eyebrows, eyelashes, and body for most of the patients. There were significant associations between the patient's age and the onset of hair regrowth in the eyebrows, eyelashes, and body. The onset of eyebrows, eyelash, and body hair growth were significantly shorter in the premenopausal patients. Any hair changes (e.g., thinned diameter, softer texture, curlier structure) were reported by 85.3% of the patients. CONCLUSIONS: Severe CIA occurred in all 68 patients who received FEC and taxane chemotherapy. The present findings provide the first data demonstrating that age was not associated with the degree or incidence of hair loss, but age affected the recovery from CIA. These results contribute more accurate information provision and insights regarding the proper treatment of CIA.

Body Composition, Adherence to Anthracycline and Taxane-Based Chemotherapy, and Survival After Nonmetastatic Breast Cancer.

Importance: Although most chemotherapies are dosed on body surface area or weight, body composition (ie, the amount and distribution of muscle and adipose tissues) is thought to be associated with chemotherapy tolerance and adherence. Objectives: To evaluate whether body composition is associated with relative dose intensity (RDI) on anthracycline and taxane-based chemotherapy or hematologic toxic effects and whether lower RDI mediates the association of adiposity with mortality. Design, Setting, and Participants: An observational cohort study with prospectively collected electronic medical record data was conducted at Kaiser Permanente Northern California, a multicenter, community oncology setting within an integrated health care delivery system. Participants included 1395 patients with nonmetastatic breast cancer diagnosed between January 1, 2005, and December 31, 2013, and treated with anthracycline and taxane-based chemotherapy. Data analysis was performed between February 25 and September 4, 2019. Exposures: Intramuscular, visceral, and subcutaneous adiposity as well as skeletal muscle were evaluated from clinically acquired computed tomographic scans at diagnosis. Main Outcomes and Measures: The primary outcome was low RDI (<0.85), which is the ratio of delivered to planned chemotherapy dose, derived from infusion records; in addition, hematologic toxic effects were defined based on laboratory test values. To evaluate associations with overall and breast cancer-specific mortality, logistic regression models adjusted for age and body surface area were fit as well as Cox proportional hazards models adjusted for age, race/ethnicity, adiposity, Charlson comorbidity index score, and tumor stage and subtype. The mediation proportion was computed using the difference method. Results: The mean (SD) age at diagnosis of the 1395 women included in the study was 52.8 (10.2) years. Greater visceral (odds ratio [OR], 1.19; 95% CI, 1.02-1.39 per SD) and intramuscular (OR, 1.16; 95% CI, 1.01-1.34 per SD) adiposity were associated with increased odds of RDI less than 0.85. Greater muscle mass was associated with a decreased odds of hematologic toxic effects (OR, 0.84; 95% CI, 0.71-0.98 per SD). Relative dose intensity less than 0.85 was associated with a 30% increased risk of death (hazard ratio, 1.30; 95% CI, 1.02-1.65). Lower RDI partially explained the association of adiposity with breast cancer-specific mortality (mediation proportion, 0.20; 95% CI, 0.05-0.55). Conclusions and Relevance: Excess adiposity, presenting as larger visceral or intramuscular adiposity, was associated with lower RDI. Lower RDI partially mediated the association of adiposity with worse breast cancer-specific survival. Body composition may help to identify patients likely to experience toxic effects and subsequent dose delays or reductions, which could compromise chemotherapeutic efficacy.

Impaired Postural Control and Altered Sensory Organization During Quiet Stance Following Neurotoxic Chemotherapy: A Preliminary Study.

Individuals diagnosed with chemotherapy-induced peripheral neuropathy (CIPN) demonstrate impaired balance and carry an increased risk of falling. However, prior investigations of postural instability have only compared these individuals against healthy controls, limiting the understanding of impairments associated with CIPN. Therefore, the purpose of this study was to better isolate postural control impairments that are associated with CIPN. Twenty cancer survivors previously diagnosed with breast or colorectal cancer participated. Participants were separated into 3 groups: no prior chemotherapy exposure (CON, n = 6), and recent treatment with taxane- or oxaliplatin-based chemotherapy with no/mild symptoms of CIPN (-CIPN, n = 8) or moderate/severe symptoms of CIPN (+CIPN, n = 6). Postural control was assessed by measuring center of pressure during standing balance conditions that systematically interfered with somatosensory, visual, and/or vestibular information. The presence of CIPN sensory symptoms was associated with impaired postural control, particularly during eyes-closed balance conditions ( P < .05). Additionally, medial-lateral postural instability was more pronounced in the +CIPN group compared with the -CIPN group and CON participants ( P < .05). Greater postural instability during eyes-closed balance in individuals with CIPN is consistent with impaired peripheral sensation. Balance impairments in cancer survivors with CIPN demonstrate the unique challenges in this population and motivate the need for targeted efforts to mitigate postural control deficits that have previously been associated with fall risk.

Annurca Apple Polyphenols Protect Murine Hair Follicles from Taxane Induced Dystrophy and Hijacks Polyunsaturated Fatty Acid Metabolism toward ß-Oxidation.

Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual interactions and causes anxiety and depression. Synthetic drugs protecting from CIA and endowed with hair growth stimulatory properties are prescribed with caution by oncologists. Hormones, growth factors, morphogens could unwontedly protect tumour cells or induce cancer cell proliferation and are thus considered incompatible with many chemotherapy regimens. Nutraceuticals, on the contrary, have been shown to be safe and effective treatment options for hair loss. We here show that polyphenols from Malus Pumila Miller cv Annurca are endowed with hair growth promoting activity and can be considered a safe alternative to avoid CIA. In vitro, Annurca Apple Polyphenolic Extract (AAE) protects murine Hair Follicles (HF) from taxanes induced dystrophy. Moreover, in virtue of its mechanism of action, AAE is herein proven to be compatible with chemotherapy regimens. AAE forces HFs to produce ATP using mitochondrial ß-oxidation, reducing Pentose Phosphate Pathway (PPP) rate and nucleotides production. As consequence, DNA replication and mitosis are not stimulated, while a pool of free amino acids usually involved in catabolic reactions are spared for keratin production. Moreover, measuring the effect exerted on Poly Unsaturated Fatty Acid (PUFA) metabolism, we prove that AAE promotes hair-growth by increasing the intracellular levels of Prostaglandins F2α (PGF2α) and by hijacking PUFA catabolites toward ß-oxidation.

Associations between self-reported diet during treatment and chemotherapy-induced peripheral neuropathy in a cooperative group trial (S0221).

BACKGROUND: The pathophysiology of chemotherapy-induced peripheral neuropathy (CIPN) is not well understood. Currently, dose reduction is the only recommendation for alleviating symptoms, often leading to premature treatment cessation. The primary aim of this analysis was to determine the association between components of diet during taxane treatment for breast cancer and change in CIPN symptoms over treatment. METHODS: Women with stage II or III invasive breast cancer were enrolled into an ancillary study to the North American Breast Cancer Intergroup phase III trial (S0221) led by the Southwest Oncology Group (SWOG). Questionnaires including a food frequency questionnaire and the Functional Assessment of Cancer Treatment Gynecologic Oncology Group-Neurotoxicity were administered to assess diet and neuropathic conditions at baseline and during chemotherapy. Ordinal regression was used to estimate odds ratios (ORs) for associations between various food groups and change in neuropathy score (< 10%, 10-30%, > 30%) (n = 900). RESULTS: The odds of worse neuropathy decreased by 21% for each increase in tertile of grain consumption (OR = 0.79, 95% CI 0.66-0.94, p = 0.009). We also observed a nominal 19% increase with higher consumption of citrus fruits (OR = 1.19, 95% CI 1.01-1.40, p = 0.05). CONCLUSIONS: Distinguishing between those who experienced a moderate and a severe change in neuropathy, we found that citrus fruit and grain consumption may play a role in the severity of symptoms. Since there are no existing dietary recommendations for the management of CIPN, further research is needed to investigate whether there may be certain foods that could worsen or alleviate neuropathy symptoms associated with treatment for breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03413761 . Registered retrospectively on 29 January 2018.

Pacritinib to treat myelofibrosis patients with thrombocytopenia.

INTRODUCTION: Treatment with ruxolitinib, a selective JAK1/2 inhibitor, has significantly improved the lives of patients with myelofibrosis. Unfortunately, this treatment is frequently limited by cytopenias, precluding a high-risk group characterized by baseline thrombocytopenia. Additionally, there are no approved treatments for patients who have progressed while receiving ruxolitinib. Pacritinib is a novel JAK2/FLT3 inhibitor associated with less treatment-related myelosuppression that has the potential to fill these unmet treatment needs. Areas covered: This review will describe the preclinical rationale for JAK2/FLT3 inhibition, review the pharmacology of pacritinib, and detail available clinical data for pacritinib treatment of myelofibrosis. The circumstances surrounding the full clinical hold temporarily placed on pacritinib will also be explored. Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia. Improvements in splenomegaly and symptom burden were observed with the 200 mg twice-daily dose in PERSIST-2, including those with platelet counts <50,000 mm. Safety concerns pertaining to cardiovascular events and bleeding that arose in an early analysis of PERSIST-2 were likely related to the advanced disease state enrolled rather than clear attribution to pacritinib. The results of an ongoing dose-finding, phase II study are eagerly awaited in order to move this promising myelofibrosis therapy forward.

Effect of a Complementary/Integrative Medicine Treatment Program on Taxane-Induced Peripheral Neuropathy: A Brief Report.

OBJECTIVE: Peripheral neuropathy is a common complication of cancer treatment impairing quality of life and function. This study explored the impact of a complementary and integrative medicine (CIM) program on taxane-induced peripheral neuropathy (TIPN). MATERIALS AND METHODS: Taxane-treated female patients with breast and gynecological cancer reporting TIPN-related symptoms were referred to an integrative physician, followed by patient-tailored CIM treatments (acupuncture with/without other modalities). Assessment of study outcomes at 6 to 12 weeks was conducted using the Measure Yourself Concerns and Wellbeing, which documented free-text narratives about patients' experience during the CIM treatment process. Content was analyzed using ATLAS.Ti software. RESULTS: Of the 125 patients treated with taxanes, 69 had been referred for CIM treatment of TIPN-associated symptoms. Multidisciplinary narrative analysis identified 2 groups of CIM-treated patients: those with an apparently moderate improvement in symptoms (n = 35) and those with either only an apparent mild or no improvement at all. For 10 patients, assessment of their response to treatment was unclear. The 2 identified groups had similar demographic, cancer-related, and quality of life-related parameters at baseline. Content analysis of patients with an apparent moderate improvement suggested a short-term (24-48 hours) effect with acupuncture treatment, either alone or combined with manual, mind-body, and anthroposophic music therapies. Symptoms showing improvement included paresthesia and numbness. CONCLUSIONS: Acupuncture and other CIM therapies may result in a short-term and transitory reduction in TIPN-related symptoms.

Reflexology in the management of chemotherapy induced peripheral neuropathy: A pilot randomized controlled trial.

PURPOSE: The current experimental study aimed to evaluate the effectiveness of reflexology on the management of symptoms and functions of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients. METHOD: This study was conducted as a randomized controlled trial in 60 patients (30 experimental and 30 control patients) who had chemotherapy-induced Grade II-IV peripheral neuropathy complaints from July 2013 to November 2015. Data were collected using the patient identification form, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC-CIPN-20) form, and BPI (used for related chemotherapy-induced peripheral neuropathy symptoms). RESULTS: The majority of the patients were being treated for gastrointestinal or breast cancer and were primarily receiving Eloxatine- or taxane-based treatment. It was found that reflexology applications did not lead to differences in either group in terms of peripheral neuropathy severity and incidence (p > 0.05) and only led to improvement in sensory functions in the experimental group (p < 0.05). CONCLUSIONS: It was determined that reflexology is not an effective method in the management of patients' activity levels, walking ability etc. and motor, autonomic functions related CIPN, but reflexology is effective method in the management of patients' sensory functions related CIPN. Key Words: Peripheral neuropathy, reflexology, chemotherapy, EORTC QLQ-CIPN-20, BPI.

BMI, Lifestyle Factors and Taxane-Induced Neuropathy in Breast Cancer Patients: The Pathways Study.

Background: Lifestyle factors may be associated with chemotherapy-induced peripheral neuropathy (CIPN). We examined associations between body mass index (BMI) and lifestyle factors with CIPN in the Pathways Study, a prospective cohort of women with invasive breast cancer. Methods: Analyses included 1237 women who received taxane treatment and provided data on neurotoxicity symptoms. Baseline interviews assessed BMI (normal: <25 kg/m2; overweight: 25-29.9 kg/m2; obese: ≥30 kg/m2), moderate-to-vigorous physical activity (MVPA) (low: <2.5; medium: 2.5-5; high: >5 hours/week) and fruit/vegetable intake (low: <35 servings/week; high: ≥35 servings/week). Baseline and six-month interviews assessed antioxidant supplement use (nonuser, discontinued, continued user, initiator). CIPN was assessed at baseline, six months, and 24 months using the Functional Assessment of Cancer Therapy-Taxane Neurotoxicity (FACT-NTX); a 10% decrease was considered clinically meaningful. Results: At baseline, 65.6% of patients in the sample were overweight or obese, 29.9% had low MVPA, 57.5% had low fruit/vegetable intake, and 9.5% reported antioxidant supplement use during treatment. In multivariable analyses, increased CIPN was more likely to occur in overweight (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.19 to 4.88) and obese patients (OR = 3.21, 95% CI = 1.52 to 7.02) compared with normal weight patients at 24 months and less likely to occur in patients with high MVPA compared with those with low MVPA at six (OR = 0.56, 95% CI = 0.34 to 0.94) and 24 months (OR = 0.43, 95% CI = 0.21 to 0.87). Compared with nonusers, patients who initiated antioxidant use during treatment were more likely to report increased CIPN at six months (OR = 3.81, 95% CI = 1.82 to 8.04). Conclusions: Obesity and low MVPA were associated with CIPN in breast cancer patients who received taxane treatment.

The Impact of Age on Quality of Life in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Comparative Analysis From the Prospective Multicenter Randomized ADEBAR trial.

BACKGROUND: Elderly breast cancer patients are affected by poorer quality of life (QoL) compared to younger patients. Because QoL has a relevant impact on guideline-adherent treatment, elderly breast cancer patients are often undertreated, especially with regard to adjuvant chemotherapy, and overall survival is decreased. Thus, understanding the impact of chemotherapy on QoL in elderly patients is crucial. This study compared QoL in patients aged < 65 years and 65 to 70 years receiving adjuvant chemotherapy as a secondary outcome in the prospective randomized multicenter ADEBAR trial. PATIENTS AND METHODS: Patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or epirubicin/fluorouracil/cyclophosphamid chemotherapy (FEC) therapy. QoL was assessed at baseline (t1), before cycle 4 FEC, and cycle 5 epirubicin/cyclophosphamid-docetaxel (EC-DOC) (t2), 4 weeks after chemotherapy (t3), and 6 weeks after radiation (t4) using the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Breast Cancer-Specific Module (QLQ-BR23). We compared patients aged < 65 years and 65 to 70 years with respect to QoL and discontinuation of chemotherapy. RESULTS: A total of 1363 patients were enrolled onto the ADEBAR trial, with 16.7% of the patients aged 65 to 70 years. In elderly patients, Eastern Cooperative Oncology Group performance status was higher and global health status and physical functioning were lower at baseline. Global health status decreased between t1 and t3 by 7 points in patients < 65 years and by 11 points in patients 65 to 70 years, and physical functioning decreased in the same period by 13.4 points in patients aged < 65 years and by 15.9 points in patients 65 to 70 years. In both groups, at t4 global health status exceeded baseline by 6 points, and physical functioning was 1.3 points under baseline in patients < 65 years old and 3 points under baseline in patients 65 to 70 years. There was a trend to more fatigue in elderly patients and to more nausea and vomiting while receiving chemotherapy in younger patients at t3. There was a higher dropout rate in patients aged 65 to 70 years (25.7%) than in patients aged < 65 years (16.2%). CONCLUSION: There were only small or trivial differences in QoL in patients aged < 65 years versus 65 to 70 years who were receiving adjuvant chemotherapy, although the dropout rate from chemotherapy was notably higher in elderly breast cancer patients.

Randomized sham-controlled pilot trial of weekly electro-acupuncture for the prevention of taxane-induced peripheral neuropathy in women with early stage breast cancer.

To investigate the effect of electro-acupuncture (EA) as a non-pharmacological intervention to prevent or reduce chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients undergoing chemotherapy of taxane. Women with stage I-III breast cancer scheduled to receive taxane therapy were randomized to receive a standardized protocol of 12 true or sham EA (SEA) weekly treatments concurrent with taxane treatment. Subjects completed the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Taxane neurotoxicity subscale (FACT-NTX), and other assessments at baseline and weeks 6, 12, and 16. A total of 180 subjects were screened, 63 enrolled and 48 completed week 16 assessments. Mean age was 50 with 25 % white, 25 % black, and 43 % Hispanic; 52 % had no prior chemotherapy. At week 12, both groups reported an increase in mean BPI-SF worst pain score, but no mean differences were found between groups (SEA 2.8 vs. EA 2.6, P = .86). By week 16, the SEA group returned to baseline, while the EA group continued to worsen (SEA 1.7 vs. EA 3.4, P = .03). The increase in BPI-SF worst pain score was 1.62 points higher in the EA group than in the SEA group at week 16 (P = .04). In a randomized, sham-controlled trial of EA for prevention of taxane-induced CIPN, there were no differences in pain or neuropathy between groups at week 12. Of concern, subjects on EA had a slower recovery than SEA subjects. Future studies should focus on EA for treatment as opposed to prevention of CIPN.

Effectiveness of an Adjuvant Chemotherapy Regimen for Early-Stage Breast Cancer: A Systematic Review and Network Meta-analysis.

IMPORTANCE: Different adjuvant chemotherapy regimens are available for early-stage breast cancer. Because conventional meta-analysis does not allow comparing all regimens, we performed a network meta-analysis to identify the most effective adjuvant chemotherapy regimen. OBJECTIVE: To find the most effective adjuvant therapy regimen for early-stage breast cancer. DATA SOURCES: We searched MEDLINE, Embase, and the Cochrane Library for articles published before June 2015; the American Society of Clinical Oncology annual meeting abstracts from January 1983 through December 2014; and the American Association for Cancer Research annual meeting abstracts from January 1916 through December 2014. Additionally, we manually searched bibliographies for related references. STUDY SELECTION: We included randomized clinical trials of adjuvant treatments for early-stage breast cancer that compared 2 or more of the following: no adjuvant chemotherapy; sequential anthracycline-cyclophosphamide and taxane (AC-T); concurrent anthracycline-cyclophosphamide and taxane (ACT); anthracycline-cyclophosphamide without taxane (AC); docetaxel and cyclophosphamide (TC); cyclophosphamide, methotrexate, and fluorouracil (CMF); and platinum-containing regimens. DATA EXTRACTION AND SYNTHESIS: We followed the PRISMA guidelines. Two investigators independently selected the articles and extracted information. Disagreements were resolved by discussion with another author. Quality was assessed by Cochrane risk-of-bias method. Data were pooled using random-effects models. MAIN OUTCOMES AND MEASURES: We used network meta-analysis to test the most effective adjuvant therapy regimen in terms of overall survival (OS) by comparing regimens listed in the National Comprehensive Cancer Network guidelines and platinum-containing regimens. RESULTS: We identified 24 trials. The TC and platinum-containing regimens had OS benefit similar to that of sequential AC-T (TC hazard ratio [HR], 0.93; 95% CI, 0.62-1.40; and platinum HR, 0.93; 95% CI, 0.66-1.31). Patients treated with CMF or AC had significantly worse OS than those treated with sequential AC-T (CMF HR, 1.56; 95% CI, 1.32-1.85; and AC HR, 1.22; 95% CI, 1.10-1.37). Platinum-containing regimens tended to be more toxic than sequential AC-T. The toxicity of TC was similar to or less than that of sequential AC-T. Meta-regression analysis showed that hormone receptor status did not impact the HRs for OS for any regimen. CONCLUSIONS AND RELEVANCE: Sequential AC-T is likely to be the most effective adjuvant therapy regimen for early-stage breast cancer regardless of hormone receptor status.

Comparison of patient reported quality of life and impact of treatment side effects experienced with a taxane-containing regimen and standard anthracycline based chemotherapy for early breast cancer: 6 year results from the UK TACT trial (CRUK/01/001).

BACKGROUND: The TACT trial (CRUK/01/001) compared adjuvant sequential FEC-docetaxel (FEC-D) chemotherapy with standard anthracycline-based chemotherapy of similar duration in women with early breast cancer. Results at a median of 5 years suggested no improvement in disease-free survival with FEC-D. Given differing toxicity profiles of the regimens, the impact on quality of life (QL) was explored. METHODS: Patients from 44 centres completed standardised QL questionnaires before chemotherapy, after cycles 4 and 8, at 9, 12, 18 and 24 months and at 6 years follow-up. Patient diaries assessed frequency, associated distress and impact on daily activity of 15 treatment related side effects. FINDINGS: 830 patients (415 FEC-D; 415 controls) contributed assessments during 0-24 months; 362 of whom participated again at 6 years. During chemotherapy, FEC-D impaired global health/QL and depression rates and significantly more QL domains than standard regimens. Novel diary card ratings highlighted significantly more distress and interference with daily activities due to FEC-D side effects compared with standard treatment. In both groups, most QL parameters returned to baseline levels by 2 years and were unchanged at 6 years. INTERPRETATION: Within expected negative effects of chemotherapy on wide ranging QL domains FEC-D patients reported greater toxicity, disruption and distress during treatment with no improvement in disease outcome at 5 years than patients receiving standard anthracycline-based chemotherapy. Findings should inform future patients of relative costs and benefits of adjuvant chemotherapy.

Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma.

OBJECTIVE: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. MATERIALS AND METHODS: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 weekly regimen with cisplatin and docetaxel as 75 mg/m 2 each, 5-FU as 1000 mg/m 2 . NACT was either given with the intent of achieving: (1) surgical resection (extensive soft tissue disease, oropharyngeal involvement, extensive disease with cartilage erosion) or (2) organ preservation (Bulky disease with inner cartilage erosion, exolaryngeal disease without cartilage erosion, large N3 nodes). RESULTS: The mean age of this population was 55 years. Most (83%) of the patients had pyriform sinus (PFS) involvement. 69% patients had Stage IVa disease, 21% Stage IVb and 10% Stage III. The overall response rate was 66%, including 06% complete responses and 60% partial responses. Following NACT, resectability was achieved in 30% (10/33) and organ preservation protocol was planned after NACT in 73% (19/26) patients. The main toxicities were neutropenia (grade 3, 4, 04%; febrile neutropenia, 4%), mucositis 5%, diarrhea 5%. The median progression free survival was 20 months. CONCLUSIONS: NACT can be useful in patients with oropharyngeal involvement to achieve surgical resection and larynx preservation in patients with bulky T3 disease.

Risk of treatment related death and febrile neutropaenia with taxane-based adjuvant chemotherapy for breast cancer in a middle income country outside a clinical trial setting.

BACKGROUND: The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC). PATIENTS AND METHODS: Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L. RESULTS: A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD. CONCLUSION: Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection.

OBJECTIVES: The DNA repair pathway and isotype composition of beta-tubulin are known to be associated with resistance to platinum- and taxane-based chemotherapy, respectively. The aim of this study was to identify the clinical significance of excision repair cross-complementation 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), X-ray repair cross-complementation 1 (XRCC1) and betaIII-tubulin on the chemotherapy response and overall survival in patients with non-small cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. METHODS: Protein expression profiles were evaluated by immunohistochemistry on surgical specimens of 82 NSCLC patients who underwent platinum- and taxane-based neoadjuvant chemotherapy. The expression levels of proteins were measured semi-quantitatively and the correlation with tumor responses, pathologic cell death rate and survival were evaluated. RESULTS: There were 73 (89.0%) clinical stage III patients. Lobectomy, bilobectomy, and pneumonectomy were performed in 54 (65.0%), 11 (13.4%), and 17 (20.7%) patients, respectively. There was no correlation between clinical response and protein expression. The expression levels of ERCC1, BRCA1, and XRCC1 increased proportionally to the cell death rate (p<0.05); however, betaIII-tubulin expression did not correlate with cell viability. Multivariate analysis demonstrated that early pathologic stage, adjuvant chemotherapy, high ERCC1 and low betaIII-tubulin expression were good prognostic factors for overall survival (p<0.05). CONCLUSIONS: The inverse correlation between DNA repair proteins and cell viability suggests that these protein expression levels can be markers for chemotherapy responsiveness. However, only ERCC1 and betaIII-tubulin were prognostic factors after platinum- and taxane-based neoadjuvant chemotherapy following surgical resection.

Hyperthermic intraperitoneal chemotherapy after extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: interim analysis of a phase II study.

BACKGROUND: The objective of the current study was to evaluate the toxicities and treatment response of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer. METHODS: Intraoperative HIPEC (cisplatin 75 mg/m(2), 41.5 degrees C, 90 min) was performed in 30 patients with residual tumor of <1 cm after cytoreductive surgery between January 2007 and February 2008. All the patients received adjuvant chemotherapy with combination platinum and taxane. Adverse events and responses to primary treatment were evaluated and scored as follows: grade I, observation; grade II, medical treatment; grade III, intervention; and grade IV, reoperation or admission to the intensive care unit. RESULTS: No deaths or grade IV morbidities were observed. One hundred seven adverse events were identified in 30 patients (grade I, 40; grade II, 46; grade III, 21). The most common adverse events affected the hematologic system (n = 26), followed by the gastrointestinal system (n = 23). Most adverse events were anemias requiring transfusion and nausea/vomiting requiring medication. Twenty-eight patients (93%) experienced complete remission, and two patients (7%) had progressive disease. CONCLUSION: HIPEC after extensive cytoreductive surgery for ovarian cancer is a procedure with acceptable morbidity that patients can tolerate. More follow-up is needed to determine the effect of HIPEC on survival.

Quantitative and clinical description of postural instability in women with breast cancer treated with taxane chemotherapy.

OBJECTIVE: To describe the postural control of women who received taxane chemotherapy for treatment of breast cancer using quantitative and clinically feasible measures. DESIGN: Prospective descriptive study. SETTING: University-based comprehensive cancer center. PARTICIPANTS: Twenty women who completed taxane treatment for breast cancer and 20 healthy controls participated in this study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Two quantitative measures of postural control were used, Sensory Organization Test (SOT) and center of pressure (COP) velocities. Two clinically feasible measures of postural control were used, the Fullerton Advanced Balance Scale (FABS) and Timed Up & Go (TUG) test. RESULTS: Compared with healthy controls, women with breast cancer had poorer postural control on all of the outcome measures. FABS and TUG scores correlated moderately with SOT and COP scores. CONCLUSIONS: After taxane chemotherapy, women with breast cancer show significantly increased postural instability compared with matched controls. Clinically feasible measures of postural control correlated with quantitative tests. These results suggest that these clinical measures may be useful to screen patients to determine who may benefit from rehabilitation.

Phase II trial of capecitabine and weekly paclitaxel in patients with metastatic breast cancer previously treated with every-3-week taxane therapy.

PURPOSE: We conducted a multicenter phase II trial to determine the efficacy/safety of capecitabine and weekly paclitaxel, a combination with preclinical evidence of synergy, in patients with metastatic breast cancer (MBC) previously treated with a taxane. PATIENTS AND METHODS: Eligibility criteria included measurable MBC, history of every-3-week taxane therapy (adjuvant or for MBC), and no previous taxane on a weekly basis, capecitabine, or infusional 5-fluorouracil. Patients received capecitabine 825 mg/m2 per dose orally twice daily (1650 mg/m2 per day) on days 1-14 and weekly paclitaxel 80 mg/m2 intravenously on days 1 and 8, followed by a 1-week rest period (every-3-week cycle) until progression or intolerable toxicity. Fifty-four women were treated, most with previous every-3-week taxane exposure as adjuvant therapy (n=43) rather than for MBC (n=11). The median number of delivered cycles was 7, with dose modifications in 30 patients. The intent-to-treat objective response rate (primary study endpoint) was 59% (95% confidence interval, 46%-72%), including 7 complete and 25 partial responses. RESULTS: Three patients had stable disease for>or=6 months, for a clinical benefit rate of 65% (95% confidence interval, 51%-76%). Median objective response duration, time to progression, and overall survival were 8.1 months, 8.4 months, and 21.6 months, respectively. Grade 3/4 treatment-related adverse events consisted of neutropenia (13%), anemia (2%), hand-foot skin reaction (20%), fatigue (7%), diarrhea (4%), nausea/vomiting (4%), and pain (2%). No patients developed grade 3/4 neuropathy. CONCLUSION: Capecitabine and weekly paclitaxel were highly active with acceptable tolerability in patients with MBC previously treated with a taxane, consistent with our recently published experience in taxane-naive women with MBC.

Drug evaluation: Bay-59-8862.

Bayer Corp, under license from Indena SpA, is developing BAY-59-8862, a taxane synthesized from 14beta-hydroxy-10-deacetylbaccatin III, for the potential treatment of cancer.