Capecitabine combined with oxaliplatin (CapOx) in clinical practice: how significant is peripheral neuropathy?

BACKGROUND: There is speculation that peripheral neuropathy (PN) with capecitabine and oxaliplatin (CapOx; 130 mg/m(2), day 1, every 21 days) may be more common than with FOLFOX4 (5-fluorouracil and oxaliplatin 85 mg/m(2), day 1, every 14 days). We aimed to determine PN incidence and associations during CapOx, and 6 and 12 months after CapOx. PATIENTS AND METHODS: Retrospective audit of 188 oxaliplatin-naive colorectal cancer patients (87 adjuvant, 101 palliative) who received at least one cycle of CapOx. Neurosensory Common Toxicity Criteria Adverse Events version 3 were applied. RESULTS: Overall, 94% experienced acute PN. Worst severities for adjuvant and palliative patients, respectively, were grade 1, 44% and 54%; grade 2, 35% and 32%; grade 3, 16% and 3%; grade 4, 0% and 1% and grade unclear 1% and 1%. Two patients developed PN after CapOx completion despite no symptoms during treatment. Chronic PN at 6 months affected 57% and 18% of adjuvant and palliative patients, respectively. At 12 months, 35% and 16% were affected. Chronic PN at 12 months was associated with cumulative oxaliplatin dose but not age, gender, acute myotonia, pseudolaryngospasm or grade 2 or more PN during treatment. CONCLUSION: Incidence of acute PN during CapOx appears similar to FOLFOX4 but chronic PN in adjuvant patients may be more common with CapOx.

Osteonecrosis of the femoral head following adjuvant chemotherapy for breast cancer.

We report a case of osteonecrosis in a patient treated with adjuvant chemotherapy for breast cancer. A 68-year-old woman presented with severe right hip pain. Seven months after completing a course of 6 cycles of adjuvant Cyclophosphamide, Methotrexate and 5-Fluorouracil with standard anti-emetic prophylaxis of Dexamethasone and Domperidone for a T2N0M0 breast cancer. Investigations revealed evidence of osteonecrosis of the right femoral head. Due to ongoing hip pain, she underwent an elective total hip replacement and her mobility has returned almost to normal. Osteonecrosis has been associated with corticosteroids and cytotoxic regimens which omit these agents. Osteonecrosis is a rare complication of cytotoxic therapy but with the increasing use of chemotherapy it should be considered in the differential diagnosis of joint pain in patients who have received anti-tumour therapies.

A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly.

The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m2. Other toxicities > or = CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t(1/2) at 180 mg/m2 = 14.1 h) and the urinary elimination of the unchanged drug was < 10%. In a patient with previously treated small cell lung carcinoma (SCLC), a 49% reduction in measurable disease was noted with resolution of pericardial and pleural effusions (120 mg/m2 x eight cycles). From the results of this phase I study a dose of 180 mg/m2 as a 1 h infusion every 3 weeks would be recommended for phase II trials.

Alcoholics' initial organizational and problem-solving skills predict learning and memory performance on the Rey-Osterrieth Complex Figure.

This study was undertaken to investigate whether alcoholics differ qualitatively from controls in their organizational approach to the Rey-Osterrieth Complex Figure (ROCF) and to examine the effects of problem-solving and organizational ability on learning and retention. Data were collected on 3 groups of neuromedically healthy, middle-aged men: 29 recently detoxified alcoholics (RDA) abstinent at least 2 weeks, 29 long-term abstinent alcoholics (LTA) abstinent at least 18 months, and 29 nonalcoholic controls (NAC). Groups were comparable in age, education, WAIS-R Vocabulary score, and ANART IQ. Three indices of problem-solving approach were used to score how participants produce the ROCF during the copy condition: perceptual clustering, organization, and constructional accuracy. Learning and retention were measured by immediate recall, 20-min delayed recall, and recognition performance. RDAs had significantly impaired immediate recall, delayed recall, and recognition scores compared to NACs. RDAs also had significantly lower perceptual clustering, organization, and constructional accuracy scores than their long-term abstinent and nonalcoholic counterparts. Multiple regression analyses revealed that problem-solving ability at copy accounted for a significant proportion of the variance in immediate recall, delayed recall, and recognition. Further investigation of memory performance using a repeated measures design revealed that across the 3 groups, little forgetting occurred between immediate and delayed recall, while performance improved significantly on the recognition trial. Use of less efficient problem-solving strategies appears to affect RDAs' ability to learn and retrieve complex figural information.

Bacterial endocarditis associated with a skin-tunnelled catheter.

Skin-tunnelled catheters have become an accepted method for establishing long-term central venous access in patients undergoing treatment for malignancies. They allow administration of continuous infusions of cytotoxic drugs, supplementation of fluids and blood products, total parenteral nutrition and access for the checking of blood tests. It is recognized that there are certain complications associated with their use including the risk of infection both of the exit site and tunnel, as a source of septicaemia, line-associated thrombosis (despite the use of prophylactic low dose warfarin and flushing of the line with heparin) and accidental dislodgement of the line. We report a case of bacterial endocarditis affecting the pulmonary valve shortly after removal of a skin-tunnelled catheter due to line-associated brachiocephalic venous thrombosis.