An open label phase 1 study evaluation safety, tolerability, and maximum tolerated dose of oral administration of irinotecan in combination with capecitabine.

PURPOSE: Oral administration of chemotherapy offers several advantages in comparison with intravenous administration. Previously, data on a new oral formulation of irinotecan have been published. The aim of the present study was to evaluate the safety, tolerability, and Maximum Tolerated Dose (MTD) of the new oral irinotecan formulation in combination with oral capecitabine. METHODS: The study was an open label, phase 1, single center, extension part in which oral irinotecan was investigated in combination with capecitabine. The MTD of irinotecan in combination with capecitabine was 17.5 mg/m2 once daily for 14 consecutive days in combination with capecitabine 800 mg/m2 twice daily. Eligible patients were adults with metastatic or unresectable solid tumors for which no standard curative or palliative therapies existed. RESULTS: 14 patients were included in the extension part. No grade 3 or 4 hematologic toxicities were observed. Non-hematological toxicities included grade 1 and 2 diarrhea, fatigue, cholinergic syndrome, vomiting, and weight loss. Totally, 3 grade 3 toxicities and no grade 4 event were reported. No objective responses were observed. Five patients had stable disease lasting median 14 weeks. CONCLUSIONS: Capecitabine in combination with oral irinotecan could be a new treatment option offering a more convenient and patient friendly treatment strategy compared to intravenous irinotecan. The combination is fairly tolerated; however, further investigations are needed to assess the efficacy of this regimen.

Urinary albumin excretion is a predictor of response to treatment and disease progression in low-grade non-Hodgkin's lymphoma.

Slightly increased urinary albumin excretion (UAE) is frequently found in patients with malignant diseases and is associated with adverse prognostic factors. In the present study, the main objective was to elucidate the role of UAE as predictor of response to treatment and time to progression in low-grade non-Hodgkin's lymphoma. We included 52 patients with newly diagnosed follicular lymphoma grade 1 and 2. Pre- and post-treatment median UAE level was 17.5 and 12.0 microg/min, respectively (P < 0.01). Significantly more patients with a pre-treatment UAE below the median level were in CR after treatment (P < 0.05). Patients with a clinical response to treatment had a significantly lower frequency of UAE above the median post-treatment level (P < 0.05). UAE at the time of progression increased to a significantly higher level compared with the post-treatment level (26.5 vs. 16.0 microg/min; P < 0.0001). Median response duration and progression-free survival were significantly longer in patients with a post-treatment UAE below the median level (P < 0.001 and P < 0.0001, respectively). In conclusion, we found elevated UAE to be a highly sensitive indicator of clinical behavior in newly diagnosed low-grade lymphoma. Both response to treatment and time to progression were predicted by levels of UAE. Further studies are needed to confirm the clinical implications of UAE in lymphoma patients.

Mediators of inflammation correlate with microalbuminuria in patients with non-Hodgkin's lymphoma.

Recent studies have demonstrated a high frequency of minor glomerular leakage of albumin in cancer patients. Pathogenic mechanisms of increased urinary albumin excretion (UAE) in malignancies remain to be clarified. We have attempted to identify whether microalbuminuria in lymphoma patients is associated with inflammatory mediators and the acute-phase response. UAE, urinary excretion of beta2-microglobulin and IgG, and serum levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) were determined in 113 patients with newly diagnosed non-Hodgkin's lymphoma. We demonstrated a high frequency of microalbuminuria (>or= 20 microg/min) and UAE correlated strongly with serum levels of CRP, IL-6 and TNF-alpha. UAE, CRP, IL-6 and TNF-alpha were significantly higher in patients with advanced disease stage, B symptoms and in high-risk patients according to the International Prognostic Index. Urinary excretion of beta2-microglobulin was unaffected in patients with increased UAE. However, UAE was significantly correlated with urinary excretion of IgG, suggesting an altered size selectivity of the glomerular filtration barrier. This is the first study that shows a direct correlation between microalbuminuria and proinflammatory cytokines in malignancies, indicating a pathogenic relationship between inflammation and glomerular leakage of albumin. Future efforts should focus on the pathophysiological cause-effect mechanisms and larger studies are needed to confirm the clinical significance of UAE.