Burden of chemotherapy-induced neuropathy--a cross-sectional study.

BACKGROUND: Neuropathy is a common adverse effect of chemotherapy. However, the both the prevalence and the burden of this adverse effect have been poorly documented. The aim of the study was to assess the prevalence and discomfort caused by neuropathic symptoms in relation to other adverse effects of chemotherapy. PATIENTS AND METHODS: Between January 2002 and June 2004, we screened 448 patients who were treated with vinca alkaloids, taxanes or platina derivatives, using a simple questionnaire of neuropathic symptoms. The response rate was 75%. Neuropathic symptoms were reported by 258 respondents (76%), of whom 152 patients were eligible for the final analyses. The severity of neuropathy was scored using the National Cancer Institute Common Toxicity Criteria. RESULTS: At the screening visit, 90 patients (59%) still reported neuropathic symptoms. Tingling (71%), numbness (58%), impaired sensory function (46%) and pain in hands and feet (40%) were the most common symptoms. The median intensity of neuropathic symptoms was 28/100 on the visual analogue scale. Grade 1 sensory neuropathy was found in 19 out of 90 patients (21%), grade 2 in 38 (42%) and grade 3 in 33 (37%) patients. Grade 1 motor neuropathy was found in 28 (31%), grade 2 in 14 (16%) and grade 3 in one patient (1%). Grade 4 sensory or motor neuropathy was not seen. In the whole cohort of 152 patients, fatigue (66%), mucositis (61%) and neuropathic symptoms (59%) were the most commonly reported symptoms. Every third patient (37%) with neuropathic symptoms ranked them as the most troublesome symptom. DISCUSSION: Neuropathy is a common and troublesome adverse effect of chemotherapy, even though the intensity of the symptoms is mild. Thus, the intensity and inconvenience does not correlate to each other.

Biweekly Cabazitaxel Is a Safe Treatment Option for Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients After Docetaxel - A Final Analysis of the Prosty II Trial.

BACKGROUND/AIM: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. PATIENTS AND METHODS: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. RESULTS: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. CONCLUSION: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.

Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms.

Neuropathy is common in patients receiving vinca alkaloids, platinum derivatives, or taxanes. This double-blind, randomized, placebo-controlled study assessed the efficacy of low-dose amitriptyline to relieve chemotherapy-induced symptoms in 44 patients (age 20-65 years) who had neuropathic symptoms (numbness, tingling, pain) with a severity of > or =3/10. They were treated with amitriptyline for eight weeks (10mg/day to start, then dose elevation of 10mg/week up to 50mg/day if tolerated, followed by a stable dose > or =4 weeks). The patients completed a diary twice weekly, noting the intensity of pain, numbness and tingling, global improvement, and adverse effects. Neurological examination was performed at each visit (baseline, four, and eight weeks). The patients assessed both intensity and relief of pain, and overall discomfort. They also completed the Neuropathic Pain Scale and validated measures of anxiety and depression, and quality of life (QoL). The results demonstrated that amitriptyline did not improve sensory neuropathic symptoms, although there was a trend toward global improvement and improved QoL in favor of the amitriptyline group. No statistical significance was reached, probably due to the small number of patients and too low dose of amitriptyline. Amitriptyline was well tolerated.

Bi-weekly paclitaxel and capecitabine as a second- or third-line treatment for advanced breast cancer: a pilot study.

BACKGROUND: Chemotherapy given every third week is currently the mainstay in the treatment of metastatic breast cancer (MBC). However, bi-weekly dosing might offer a better dose intensity, with better tolerability and response rates. This hypothesis was tested in a phase II study on bi-weekly paclitaxel combined with capecitabine. PATIENTS AND METHODS: Nineteen patients [median age was 60 (range: 43-68) years] with MBC were treated with paclitaxel (Taxol(®)) 120 mg/m(2), with 1-h infusion on days 1 and 15, and capecitabine (Xeloda(®)) 2650 mg/m(2)/day orally given at two doses on days 1-7 and 15-21 on a 28-day cycle. Metastatic sites included the bone (68%), lung (63%) and liver (47%), and 95% of patients had more than one sites of metastasis. RESULTS: In the response evaluation, one complete and 12 partial responses (overall response rate 68%), two stable disease cases and two progressive disease cases were observed. The median duration of response was 13.4 (range: 3.9-43.5) months. Progression-free and overall survival were 13 (95% CI=10.8-15.3) months and 23 (95% CI=17.7-29.1), respectively. A total of 140 (median 8, range 1-28) cycles were delivered. Grade 3-4 toxicity was uncommon: neutropenia was observed in 5% of the cycles; pulmonary problems in 1.4%; pain in 1.4%; and hand-and-foot syndrome, tiredness and arthralgia/myalgia, each in 0.7% of the study treatment cycles. CONCLUSION: Bi-weekly dosing of paclitaxel and capecitabine seems to yield promising responses in advanced breast cancer, with an acceptable adverse-event profile.

Oxaliplatin scale and National Cancer Institute-Common Toxicity Criteria in the assessment of chemotherapy-induced peripheral neuropathy.

AIM: The aim of the study was to compare two different neurotoxicity scales in grading chemotherapy-induced neurotoxicity. PATIENTS AND METHODS: The study sample consisted of 114 cancer patients who started chemotherapy with vinca alcaloids, platinum derivatives or taxanes. Neurotoxicity was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) and oxaliplatin scales at baseline and after every third chemotherapy cycle thereafter. RESULTS: Neuropathy was detected in 60%, 55% and 75% at the second, third and fourth visits, respectively, with the NCI-CTC sensory scale and 59%, 55% and 80% with the oxalipalatin scale. Of the patients with grade 3-4 toxicity on the oxaliplatin scale, 23/53 had grade 1, 18/53 had grade 2 and 12/53 had grade 3 neurotoxicity on the NCI-CTC sensory scale. CONCLUSION: The oxaliplatin and NCI-CTC sensory scales were comparable in identifying chemotherapy-induced neuropathy, but the oxaliplatin scale more often detected the progression of the symptoms.

Intraepidermal nerve fibre density in cancer patients receiving adjuvant chemotherapy.

BACKGROUND: Chemotherapy-induced neuropathy is a common adverse event in patients receiving vinca alcaloids, platinum derivatives and taxanes. However, the underlying pathogenetic mechanisms have not been completely elucidated. We set up a prospective pilot study on skin biopsies in newly diagnosed cancer patients receiving neurotoxic chemotherapeutic agents as adjuvant treatment in order to study the occurrence of small-fibre pathology and its relationship to clinical symptoms. PATIENTS AND METHODS: Skin biopsies from distal leg were performed in 12 patients before, during and after chemotherapy. Using light microscopy, the intraepidermal nerve fibre (IENF) density was determined from the skin biopsies by counting morphometrically the immunopositive nerves per epidermal area. RESULTS: Reduced IENF density was observed in eight patients at baseline. During the follow-up, the IENF density increased significantly in six patients and remained unchanged in two. In four patients, the IENF density was normal both at baseline and at the end of the follow-up period. Neuropathic symptoms were manifested in nine patients, but no association with the IENF count was found. CONCLUSION: During chemotherapy, results from patients revealed different evolutionary patterns of IENF density, but symptoms and IENF density were not related.

Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms.

BACKGROUND: Neuropathy is a common adverse effect of chemotherapy. The tricyclic antidepressant, amitriptyline, is a gold standard in the treatment of neuropathic pain. This double-blind, randomized placebo-controlled trial assessed the efficacy of amitriptyline to prevent chemotherapy-induced neuropathic symptoms. PATIENTS AND METHODS: Patients without previous neuropathy, who started chemotherapy with vinca alcaloids, platina derivatives or taxanes, were randomized to receive amitriptyline (target dose, 100 mg daily) or placebo for the duration of their chemotherapy. Chemotherapy-induced neuropathic symptoms were evaluated with a patient diary and after every third chemotherapy cycle with clinical examination. The diary data were transformed to a neuropathy score. A total of 114 patients fulfilling the inclusion criteria were randomly assigned to the treatment or control arm. RESULTS: There was no difference in the appearance of chemotherapy-induced neuropathic symptoms between the groups. In general, the intensity of neuropathic symptoms was mild. CONCLUSION: Amitriptyline does not prevent chemotherapy-induced neuropathy.