To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.

Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab. The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone. (ClinicalTrials.gov number, NCT00079066.)

Cetuximab improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed. (ClinicalTrials.gov number, NCT00079066 [ClinicalTrials.gov].).

Genitourinary small cell carcinoma has a poor prognosis, which is worse in prostatic than bladder disease. Patient and tumor characteristics were not determinants of survival when prostatic and bladder small cell carcinoma were analyzed individually. For prostatic disease only primary surgical therapy was associated with prolonged survival, while for bladder disease cisplatin chemotherapy was associated with a favorable prognosis. We recommend considering primary surgical therapy for prostatic and cisplatin based chemotherapy for bladder small cell carcinoma.

The incremental cost-effectiveness ratio of cetuximab over best supportive care alone in unselected advanced colorectal cancer patients is high and sensitive to drug cost. Incremental cost-effectiveness ratios were lower when the analysis was limited to patients with wild-type KRAS tumors.

.17 demonstrated the antiepidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab improves overall and progression-free survival in patients with advanced, chemotherapy-refractory colorectal cancer (CRC), particularly in patients with wild-type KRAS tumors. This article reports the health-related quality-of-life (HRQL) outcomes from CO.17. Patients and MethodsPatients (N ϭ 572) with pretreated EGFR-detectable advanced CRC were randomly assigned to cetuximab and best supportive care (BSC) or to BSC alone. HRQL primary end points assessed by the EORTC QLQ-C30 were physical function (PF) and global health status (GHS); mean changes from baseline to 8 and 16 weeks were assessed. Post hoc analysis by KRAS mutation status was performed. ResultsQuestionnaire compliance was 94% at baseline, but it declined differentially (67% v 47% for cetuximab v BSC at 16 weeks). PF change scores were Ϫ3.9 for cetuximab and Ϫ8.6 for BSC (P ϭ .046) at 8 weeks and were Ϫ5.9 and Ϫ12.5 for cetuximab and BSC, respectively, (P ϭ .027) at 16 weeks. GHS change scores were Ϫ0.5 and Ϫ7.1 (P ϭ .008) at 8 weeks and were Ϫ3.6 and Ϫ15.2 (P ϭ .008) at 16 weeks for cetuximab and BSC, respectively. In patients who had tumors with wild-type KRAS status, cetuximab resulted in less PF deterioration at 8 weeks (Ϫ0.7 v Ϫ7.2; P ϭ .11) and 16 weeks (Ϫ3.4 v Ϫ13.8; P ϭ .008) compared with BSC. Patients with wild-type status who received cetuximab experienced improved GHS at 8 weeks, whereas patients who received BSC alone deteriorated (3.2 v Ϫ7.7; P ϭ .002). Cetuximab preserved GHS at 16 weeks (Ϫ0.2 v Ϫ18.1; P Ͻ .001). No significant differences were noted between study arms for patients with mutated KRAS tumors. ConclusionCetuximab offers important HRQL and survival benefits for pretreated patients with advanced, wild-type KRAS CRC.

Health-related quality-of-life (HRQoL) data are often included in Phase III clinical trials. We evaluate and classify the value added to Phase III trials by HRQoL outcomes, through a review of the National Cancer Institute of Canada Clinical Trials Group clinical trials experience within various cancer patient populations. HRQoL may add value in a variety of ways, including the provision of data that may contrast with or may support the primary study outcome; or that assess a unique perspective or subgroup, not addressed by the primary outcome. Thus, HRQoL data may change the study's interpretation. Even in situations where HRQoL measurement does not alter the clinical interpretation of a trial, important methodologic advances can be made. A classification of the added value of HRQoL information is provided, which may assist in choosing trials for which measurement of HRQoL outcomes will be beneficial.

Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumour and haematological malignancies, including cancers of the testes, ovary, bladder, head and neck, oesophagus, stomach and lung, as well as lymphoma and osteosarcoma. Its non-specific targeting commonly results in adverse effects and toxicities affecting the gastrointestinal, renal, neurological and haematological systems even when administered at standard doses. Since cisplatin-related toxicities are dose-dependent, these may be more pronounced in the setting of a cisplatin overdose, resulting in significant morbidity and/or mortality. The incidence of cisplatin overdoses is unknown; however, early-phase clinical trials utilizing high-dose cisplatin, and case reports in the overdose setting have characterized the clinical features associated with cisplatin overdoses, highlighting some therapeutic strategies for consideration. To date, no published guidelines exist for managing a cisplatin overdose. The major toxicities of a cisplatin overdose include nausea and vomiting, renal insufficiency, electrolyte abnormalities, myelosuppression, ototoxicity, peripheral neuropathy, hepatotoxicity and retinopathy. Diarrhoea, pancreatitis, seizures and respiratory failure have also been reported. No specific antidote for cisplatin exists. Key management principles and strategies to lessen toxicities include renoprotection and enhancing drug elimination with aggressive intravenous hydration with or without the use of an osmotic diuretic, and avoidance of nephrotoxic medications. Sodium thiosulfate and plasmapheresis, with or without haemodialysis support, should be strongly considered. Close monitoring of clinical and laboratory parameters, and institution of supportive therapies, including antiemetics and haematopoietic colony stimulating factor support, are warranted. Based on the current literature, experimental therapies such as amifostine, ditiocarb sodium (diethyldithiocarbamate), acetylcysteine, fosfomycin and colestipol are of limited clinical effectiveness and remain investigational. This review serves to highlight the clinical spectrum of toxicities resulting from a cisplatin overdose, to critically appraise the available literature and to present a suggested algorithmic approach for the initial management of a cisplatin overdose.