Purpose: National Cancer Institute of Canada Clinical Trials Group CO.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 Methods: Patients (N = 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. Results: Questionnaire compliance was 94% at baseline, but it declined differentially (67% v 47% for cetuximab v BSC at 16 weeks). PF change scores were −3.9 for cetuximab and −8.6 for BSC (P = .046) at 8 weeks and were −5.9 and −12.5 for cetuximab and BSC, respectively, (P = .027) at 16 weeks. GHS change scores were −0.5 and −7.1 (P = .008) at 8 weeks and were −3.6 and −15.2 (P = .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 (−0.7 v −7.2; P = .11) and 16 weeks (−3.4 v −13.8; P = .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 −7.7; P = .002). Cetuximab preserved GHS at 16 weeks (−0.2 v −18.1; P < .001). No significant differences were noted between study arms for patients with mutated KRAS tumors. Conclusion: Cetuximab offers important HRQL and survival benefits for pretreated patients with advanced, wild-type KRAS CRC.

The staging of colorectal cancer currently depends on pathological examination of the surgical specimen and regional lymph nodes, accompanied by imaging tests such as computed tomography (CT) scanning. However, alternative molecular methods to detect circulating tumour cells in blood or bone marrow may provide additional information about the extent of disease and prognosis. We have previously reported the development of a reverse-transcriptase polymerase chain reaction (RT-PCR) for cytokeratin 20 (CK 20) mRNA to detect circulating epithelial tumour cells. In this study, we report on the application of this method for detecting circulating tumour cells in patients with colorectal cancer. Using this method, CK 20 mRNA was detected in 8/8 human colorectal cancer cell lines, in 8/9 biopsies from primary colorectal tumours and in 9/10 biopsies of liver metastasis in patients with metastatic colorectal cancer, suggesting that CK 20 may be a useful target for the detection of circulating tumour cells in this patient group. In spiking experiments, 10 cells were consistently identified in 2 ml of whole blood (1 × 10⁶–1 × 10⁷mononuclear cells). In 12/25 (48%) peripheral blood samples from patients with known metastatic colorectal cancer, CK 20 mRNA was detected. However, there was no correlation between the detection of CK 20 mRNA in the peripheral blood and disease progression and survival in this group of patients. CK 20 mRNA was detected in 1/12 normal blood samples, which raises questions about the absolute specificity of CK 20 expression. Int. J. Cancer (Pred. Oncol.) 79:288–293, 1998.

Exercise interventions during adjuvant cancer therapy have been shown to increase functional capacity, relieve fatigue and distress and may assist rates of chemotherapy completion. These studies have been limited to breast, gastric and mixed cancer groups and it is not yet known if a similar intervention is even feasible among women with ovarian cancer. We aimed to assess safety, feasibility and potential effect of a walking intervention in women undergoing chemotherapy for ovarian cancer. Women newly diagnosed with ovarian cancer were recruited to participate in an individualised walking intervention throughout chemotherapy and were assessed pre- and post-intervention. Feasibility measures included session adherence, compliance with exercise physiologist prescribed walking targets and self-reported program acceptability. Changes in objective physical functioning (6-minute walk test), self-reported distress (Hospital Anxiety and Depression Scale), symptoms (Memorial Symptom Assessment Scale - Physical) and quality of life (Functional Assessment of Cancer Therapy - Ovarian) were calculated, and chemotherapy completion and adverse intervention effects recorded. Seventeen women were enrolled (63% recruitment rate). Mean age was 60 years (SD = 8 years), 88% were diagnosed with FIGO stage III or IV disease, 14 women underwent adjuvant and three neo-adjuvant chemotherapy. On average, women adhered to > 80% of their intervention sessions and complied with 76% of their walking targets, with the majority walking four days a week at moderate intensity for 30 minutes per session. Meaningful improvements were found in physical functioning, physical symptoms, physical well-being and ovarian cancer-specific quality of life. Most women (76%) completed ≥85% of their planned chemotherapy dose. There were no withdrawals or serious adverse events and all women reported the program as being helpful. These positive preliminary results suggest that this walking intervention for women receiving chemotherapy for ovarian cancer is safe, feasible and acceptable and could be used in development of future work. ACTRN12609000252213

Purpose: This phase I study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 [a humanized anti–Lewis Y (Le^y) antibody conjugated with calicheamicin in patients with advanced cancers expressing the Le^y antigen. Experimental Design: The primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. Secondary objectives included response rates and change in tumor metabolism. Patients with progressive, measurable, and Le^y positive malignancies were eligible for enrollment in one of two dose cohorts, 1.0 and 2.6 mg/m². The first cycle was trace labeled with ¹¹¹In for biodistribution assessment using γ camera imaging. Subsequent cycles were administered every 3 weeks up to a maximum of six cycles, depending on toxicity and response. Pharmacokinetic analysis was based on radioassay and ELISA. Results: Nine patients were enrolled in the study. Biodistribution images showed initial blood pool activity, followed by markedly increased hepatic uptake by day 2, and fast blood clearance in all patients. There was low uptake in tumor in all patients. The overall T½β of ¹¹¹In-CMD-193 was 102.88 ± 35.67 hours, with no statistically significant difference between the two dose levels. One patient had a partial metabolic response on ¹⁸F-fluorodeoxyglucose-positron emission tomography (¹⁸F-FDG PET) after four cycles, but no radiological responses were observed. Myelosuppression and effects on liver function were the most significant adverse effects. Conclusions: CMD-193 shows rapid blood clearance and increased hepatic uptake compared with prior studies of the parental antibody hu3S193. These results highlight the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics to assist in clinical development. (Clin Cancer Res 2009;15(21):6709–15)