A phase II study of capecitabine and oxaliplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract.

BACKGROUND: Advanced biliary tract carcinomas are associated with a poor prognosis, and palliative chemotherapy has only modest benefit. This multi-centre phase II study was conducted to determine the efficacy of capecitabine in combination with oxaliplatin in patients with inoperable gall bladder or biliary tract cancer. METHODS: This was a Phase II, non-randomised, two-stage Simon design, multi-centre study. Ethics approval was sought and obtained by the North West MREC, and then locally by the West Glasgow Hospitals Research Ethics Committee. Eligible patients with inoperable locally advanced or metastatic adenocarcinoma of the gall bladder or biliary tract and with adequate performance status, haematologic, renal, and hepatic function were treated with capecitabine (1000 mg/m(2) po, twice daily, days 1-14) and oxaliplatin (130 mg/m(2) i.v., day 1) every 3 weeks for up to six cycles. The primary objective of the study was to determine the objective tumour response rates (complete and partial). The secondary objectives included assessment of toxicity, progression-free survival, and overall survival. RESULTS: Forty-three patients were recruited between July 2003 and December 2005. The regimen was well tolerated with no grade 3/4 neutropenia or thrombocytopenia. Grade 3/4 sensory neuropathy was observed in six patients. Two-thirds of patients received their chemotherapy without any dose delays. Overall response rate was 23.8% (95% CI 12.05-39.5%). Stable disease was observed in a further 13 patients (31%) and progressive disease observed in 12 (28.6%) of patients. The median progression-free survival was 4.6 months (95% CI 2.8-6.4 months; Fig. 1) and the median overall survival 7.9 months (95% CI 5.3-10.4 months; Fig. 2). Fig. 1 Progression-free survival Fig. 2 Overall survival CONCLUSION: Capecitabine combined with oxaliplatin has a lower disease control and shorter overall survival than the combination of cisplatin with gemcitabine which has subsequently become the standard of care in this disease. However, capecitabine in combination with oxaliplatin does have modest activity in this disease, and can be considered as an alternative treatment option for patients in whom cisplatin and/or gemcitabine are contra-indicated.

Capecitabine combined with oxaliplatin (CapOx) in clinical practice: how significant is peripheral neuropathy?

BACKGROUND: There is speculation that peripheral neuropathy (PN) with capecitabine and oxaliplatin (CapOx; 130 mg/m(2), day 1, every 21 days) may be more common than with FOLFOX4 (5-fluorouracil and oxaliplatin 85 mg/m(2), day 1, every 14 days). We aimed to determine PN incidence and associations during CapOx, and 6 and 12 months after CapOx. PATIENTS AND METHODS: Retrospective audit of 188 oxaliplatin-naive colorectal cancer patients (87 adjuvant, 101 palliative) who received at least one cycle of CapOx. Neurosensory Common Toxicity Criteria Adverse Events version 3 were applied. RESULTS: Overall, 94% experienced acute PN. Worst severities for adjuvant and palliative patients, respectively, were grade 1, 44% and 54%; grade 2, 35% and 32%; grade 3, 16% and 3%; grade 4, 0% and 1% and grade unclear 1% and 1%. Two patients developed PN after CapOx completion despite no symptoms during treatment. Chronic PN at 6 months affected 57% and 18% of adjuvant and palliative patients, respectively. At 12 months, 35% and 16% were affected. Chronic PN at 12 months was associated with cumulative oxaliplatin dose but not age, gender, acute myotonia, pseudolaryngospasm or grade 2 or more PN during treatment. CONCLUSION: Incidence of acute PN during CapOx appears similar to FOLFOX4 but chronic PN in adjuvant patients may be more common with CapOx.

Clinically relevant fatigue in cancer outpatients: the Edinburgh Cancer Centre symptom study.

BACKGROUND: Fatigue is associated with cancer and its treatment but we know little about how many and which patients suffer fatigue of clinical severity. We aimed to determine the prevalence of clinically relevant fatigue (CRF) and its associations in outpatients with various cancer diagnoses. PATIENTS AND METHODS: A survey of outpatients with colorectal, breast, gynaecological, genitourinary, sarcoma, melanoma and miscellaneous tumours at a regional cancer centre. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) fatigue subscale and the Hospital Anxiety and Depression Scale (HADS). These self-report data were linked to demographic and clinical variables. Data were available on 2867 outpatients. RESULTS: The prevalence of CRF (EORTC fatigue subscale > or =40) was 32% (95% confidence interval 31-34%). The variables independently associated with CRF were primary cancer site, having disease present, type of cancer treatment and emotional distress (total HADS score > or =15). Emotional distress had the strongest association with fatigue but half the cases of CRF were not distressed. CONCLUSION: CRF is common in cancer outpatients and is associated with type of disease and treatment, as well as with emotional distress. The association between CRF and emotional distress is strong but they are not equivalent conditions.