Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

Contains fulltext : 79995.pdf (publisher's version ) (Open Access)BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. METHODS: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome. RESULTS: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.

An assisted structured reflection on life events and life goals in advanced cancer patients: Outcomes of a randomized controlled trial (Life InSight Application (LISA) study)

Background: Diagnosis and treatment of incurable cancer as a life-changing experience evokes difficult existential questions. Aim: A structured reflection could improve patients’ quality of life and spiritual well-being. We developed an interview model on life events and ultimate life goals and performed a randomized controlled trial to evaluate the effect thereof on quality of life and spiritual well-being. Design: The intervention group had two consultations with a spiritual counselor. The control group received care as usual. EORTC QLQ-C15-PAL and the FACIT-sp were administered at baseline and 2 and 4 months after baseline. Linear mixed model analysis was performed to test between-group differences over time. Participants: Adult patients with incurable cancer and a life expectancy ⩾6 months were randomized in a 1:1 ratio to the intervention or control group. Results: A total of 153 patients from six different hospitals were included: 77 in the intervention group and 76 in the control group. Quality of life and spiritual well-being did not significantly change over time between groups. The experience of Meaning/Peace was found to significantly influence quality of life (β = 0.52, adj. R2 = 0.26) and satisfaction with life (β = 0.61, adj. R2 = 0.37). Conclusion: Although our newly developed interview model was well perceived by patients, we were not able to demonstrate a significant difference in quality of life and spiritual well-being between groups. Future interventions by spiritual counselors aimed at improving quality of life, and spiritual well-being should focus on the provision of sources of meaning and peace

An assisted structured reflection on life events and life goals in advanced cancer patients : Outcomes of a randomized controlled trial (Life InSight Application (LISA) study)

BACKGROUND:: Diagnosis and treatment of incurable cancer as a life-changing experience evokes difficult existential questions. AIM:: A structured reflection could improve patients' quality of life and spiritual well-being. We developed an interview model on life events and ultimate life goals and performed a randomized controlled trial to evaluate the effect thereof on quality of life and spiritual well-being. DESIGN:: The intervention group had two consultations with a spiritual counselor. The control group received care as usual. EORTC QLQ-C15-PAL and the FACIT-sp were administered at baseline and 2 and 4 months after baseline. Linear mixed model analysis was performed to test between-group differences over time. PARTICIPANTS:: Adult patients with incurable cancer and a life expectancy ⩾6 months were randomized in a 1:1 ratio to the intervention or control group. RESULTS:: A total of 153 patients from six different hospitals were included: 77 in the intervention group and 76 in the control group. Quality of life and spiritual well-being did not significantly change over time between groups. The experience of Meaning/Peace was found to significantly influence quality of life ( β = 0.52, adj. R2 = 0.26) and satisfaction with life ( β = 0.61, adj. R2 = 0.37). CONCLUSION:: Although our newly developed interview model was well perceived by patients, we were not able to demonstrate a significant difference in quality of life and spiritual well-being between groups. Future interventions by spiritual counselors aimed at improving quality of life, and spiritual well-being should focus on the provision of sources of meaning and peace

An assisted structured reflection on life events and life goals in advanced cancer patients:Outcomes of a randomized controlled trial (Life InSight Application (LISA) study)

BACKGROUND:: Diagnosis and treatment of incurable cancer as a life-changing experience evokes difficult existential questions. AIM:: A structured reflection could improve patients' quality of life and spiritual well-being. We developed an interview model on life events and ultimate life goals and performed a randomized controlled trial to evaluate the effect thereof on quality of life and spiritual well-being. DESIGN:: The intervention group had two consultations with a spiritual counselor. The control group received care as usual. EORTC QLQ-C15-PAL and the FACIT-sp were administered at baseline and 2 and 4 months after baseline. Linear mixed model analysis was performed to test between-group differences over time. PARTICIPANTS:: Adult patients with incurable cancer and a life expectancy ⩾6 months were randomized in a 1:1 ratio to the intervention or control group. RESULTS:: A total of 153 patients from six different hospitals were included: 77 in the intervention group and 76 in the control group. Quality of life and spiritual well-being did not significantly change over time between groups. The experience of Meaning/Peace was found to significantly influence quality of life ( β = 0.52, adj. R2 = 0.26) and satisfaction with life ( β = 0.61, adj. R2 = 0.37). CONCLUSION:: Although our newly developed interview model was well perceived by patients, we were not able to demonstrate a significant difference in quality of life and spiritual well-being between groups. Future interventions by spiritual counselors aimed at improving quality of life, and spiritual well-being should focus on the provision of sources of meaning and peace

High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial

Abstract Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23–1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03–0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30–3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24–87%), 71% (95% CI 48–100%) and 88% (95% CI 74–100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069