Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP. Clinical benefit in a real-world study.

AIM: Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. PATIENTS AND METHODS: Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. RESULTS: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. CONCLUSION: The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

[FDG-PET/CT in staging of breast carcinoma: use in tumour stage III and locoregional recurrent breast carcinoma]. / FDG-PET/CT bij stadiëring van mammacarcinoom: toepassing bij tumorstadium III en locoregionaal recidief.

In stage III breast carcinoma, metastasized disease needs to be determined. In the past, conventional imaging by liver ultrasound, chest X-ray and bone scintigraphy was the work-up of choice. Recently, FDG-PET/CT was found to have additional value, but clinicians are hesitant to introduce this technique. We present three patients in whom FDG-PET/CT was applied. A 61-year-old woman with stage III breast carcinoma after conventional work-up was upstaged to stage IV breast carcinoma by FDG-PET/CT, upon which her treatment was changed. A 55-year-old woman suspected of stage IV breast carcinoma after conventional imaging was downstaged to stage III after FDG-PET/CT. Her treatment was changed as well. In a 78-year-old woman with recurrent breast carcinoma, the diagnostic certainty of stage III breast carcinoma was increased by FDG-PET/CT. We conclude that FDG-PET/CT is valuable for adequately diagnosing metastases in patients with stage III breast carcinoma and can replace conventional imaging.

Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

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.)

Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial.

BACKGROUND: The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than sequential administration of the same drugs in patients with advanced colorectal cancer. METHODS: We randomly assigned 820 patients with advanced colorectal cancer to receive either first-line treatment with capecitabine, second-line irinotecan, and third-line capecitabine plus oxaliplatin (sequential treatment; n=410) or first-line treatment capecitabine plus irinotecan and second-line capecitabine plus oxaliplatin (combination treatment; n=410). The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov with the number NCT00312000. FINDINGS: 17 patients (nine in the sequential treatment group, eight in the combination group) were found to be ineligible and were excluded from the analysis. 675 (84%) patients died during the study: 336 in the sequential group and 339 in the combination group. Median overall survival was 16.3 (95% CI 14.3-18.1) months for sequential treatment and 17.4 (15.2-19.2) months for combination treatment (p=0.3281). The hazard ratio for combination versus sequential treatment was 0.92 (95% CI 0.79-1.08; p=0.3281). The frequency of grade 3-4 toxicity over all lines of treatment did not differ significantly between the two groups, except for grade 3 hand-foot syndrome, which occurred more often with sequential treatment than with combination treatment (13%vs 7%; p=0.004). INTERPRETATION: Combination treatment does not significantly improve overall survival compared with the sequential use of cytotoxic drugs in advanced colorectal cancer. Thus sequential treatment remains a valid option for patients with advanced colorectal cancer.