We present a retrospective analysis of Hickman line use and associated complications in patients with solid tumours undergoing treatment with infusional chemotherapy. One hundred and ten lines were inserted in 94 patients (55 females and 39 males, median age 51), of whom 107 were placed under radiological screening, the remainder by a surgical approach. Catheters were in situ for a total of 9670 days (median 101 days, range 1-278). Fifty-five complications occurred during the lifespan of 39 catheters (35.5%), giving an overall complication rate of 4.03/1000 catheter days. Early complications included pneumothorax (4%), arterial puncture (1%) and failure of placement (1%). Late complications included sepsis (superficial and systemic) (24.5%), venous thrombosis (9%), line displacement (10%) and catheter blockage (1%). Fifteen episodes of systemic sepsis occurred in 12 patients, giving an overall sepsis rate of 1.55/1000 catheter days, while complications requiring catheter removal occurred in 20 cases (18% of insertions, 2.07/1000 catheter days). We conclude that the use of Hickman catheters as a means of long-term venous access in infusional chemotherapy patients is generally safe, but is associated with significant morbidity.

e14584 Background: GSK1120212 is a potent and highly selective inhibitor of MEK1, a component of the MAP kinase pathway. GSK1120212 demonstrates efficient inhibition of p-ERK which correlates with inhibition of cell proliferation and induction of apoptosis. PO administration of GSK1120212 achieved tumor regression in multiple mouse xenograft models. The objectives of this study are to define the maximum tolerated dose (MTD) and to evaluate the pharmacokinetics (PK) and pharmacodynamic (PD) effects of GSK1120212. Methods: In Part 1, patients (pts) with solid tumors or lymphoma are enrolled in successive cohorts and receive a single PO dose of GSK1120212 followed by QD doses on days 1 - 21 of each 28-day cycle. Tumor response is assessed Q 8 weeks. PK blood samples are collected from all pts. Ophthalmic exams are administered at baseline and as clinically warranted. Dose escalation occurs via an accelerated titration followed by a standard 3+3 escalation. In Part 2, pts with pancreatic or K-Ras mutant CRC will be enrolled at the MTD. In Part 3, pts with biopsiable tumors will enroll at MTD and sub-MTD doses. Tumor biopsies will be taken pre- and post-dose to measure pERK and other markers of cell proliferation. Results: Six pts with advanced malignancies (neuroendocrine, thyroid, colorectal (n=2), melanoma (n=2) have been treated with tablets at four dose levels: 0.125 (n=2), 0.25 (n=1), 0.5 (n=2), and 1.0 mg (n=1). No DLTs or grade 2 toxicities have been reported. One patient was on study for over 17 weeks. Based on mean AUC and Cmax, GSK1120212 exposures following 15 days of repeat-dose administration were approximately dose proportional across the dose range (0.125–0.5 mg) with a median Tmax of approximately 1.5 hours. Conclusions: GSK1120212 has been well tolerated to date. Dose escalation is ongoing. [Table: see text]

The fluorinated pyrimidines have been an important part of cancer treatment since the introduction of 5-fluorouracil several decades ago. Capecitabine is an oral fluoropyrimidine which is converted to 5-fluorouracil primarily in tumor tissue, and has the advantages of ease-of-administration, acceptable toxicity and significant antineoplastic activity. It is currently the only oral fluoropyrimidine approved for use in USA, and has an established role as monotherapy in the treatment of metastatic breast and colorectal cancers. Moreover, the addition of capecitabine to docetaxel in anthracycline-pretreated metastatic breast cancer significantly improved overall survival. The toxicity profile of capecitabine includes hand-foot syndrome, stomatitis and diarrhea, with minimal hematologic side effects. The combination of capecitabine with other anticancer agents is currently being investigated. The focus of the present article will be the role of capecitabine in the treatment of colorectal cancer.

The docetaxel–carboplatin combination is active and well tolerated in patients with epithelial ovarian cancer. We added epirubicin to this combination to investigate additional benefits of anthracyclines in epithelial ovarian cancer. Twenty-one patients, FIGO Ic-IV, performance status 0–1, were treated in four dose cohorts. Docetaxel was fixed at 75 mg m −2 , carboplatin doses were AUC 4–5 and epirubicin doses were 50–60 mg m −2 . Drugs were given on day 1, every 3 weeks, except in cohort 3, where epirubicin was given on day 8. Dexamethasone was given prophylactically. One dose-limiting toxicity occurred in cohorts 1, 2 and 4, two occurred in cohort 3. Complicated neutropenia occurred in two patients in cohorts 1 and 2 and one patient in cohorts 3 and 4. Two patients experienced grade III diarrhoea or stomatitis in cohort 1 and two in cohort 3. There were no treatment-related deaths. Grade II sensory neuropathy occurred in one patient. No cardiac toxicity or significant oedema was observed. The overall response rate was 36%, and 62% were CA125 responders. The predefined maximum tolerated dose was exceeded in cohort 3. The cohort 4 dose level (epirubicin 50 mg m −2 , carboplatin AUC 4, docetaxel 75 mg m −2 ), warrants further study.

Acute tumour lysis syndrome (TLS), a condition resulting from rapid destruction of tumour cells with massive release of cellular breakdown products, has been described following the treatment of various malignancies. However, spontaneous TLS has been described only rarely. Germ cell tumours (GCT) have a rapid cell turnover and often present with bulky metastatic disease. We report two cases of patients with metastatic GCT presenting with acute renal failure attributable to spontaneous TLS. All clinical and biochemical features of the syndrome were present. Both patients were treated with haemodialysis and intravenous administration of single-agent etoposide between dialysis sessions, resulting in recovery of renal function and marked decrease in tumour bulk within the first week after presentation. These cases are the first reported instances of spontaneous TLS in poor-risk metastatic GCT. Successful treatment with dialysis and chemotherapy is possible, and prophylactic vigorous hydration and allopurinol may be warranted in this setting.