Intensified Neoadjuvant Chemoradiotherapy for Patients with Potentially Resectable Esophageal Cancer: A Retrospective Cohort Study.

BACKGROUND: Neoadjuvant treatment consisting of five cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy), followed by esophagectomy, is the standard treatment for resectable esophageal cancer in The Netherlands. It remains unclear whether intensification of neoadjuvant therapy leads to better outcomes. This study analyzed the outcomes of intensified chemoradiotherapy. METHODS: We included patients who were deemed eligible for esophagectomy between January 2008 and December 2014. Neoadjuvant therapy consisted of six cycles of carboplatin (area under the curve = 2 mg/mL/min) and paclitaxel (50 mg/m2 of body surface area) and concurrent radiotherapy (50.4 Gy administered in 28 fractions of 1.8 Gy each, 5 days per week), followed by esophagectomy. RESULTS: Of the 176 patients included in this study, 73% underwent a resection. At a median follow-up of 29.3 months for the total cohort, median disease-free survival (DFS) was 22.5 months. DFS at 3 and 5 years was 42% and 36%, respectively, while the overall survival (OS) rates were 47% and 38%, respectively. In addition, the 5-year DFS and OS rates of our resection group were 44% and 48%, respectively. In 102 patients (58%), grade 3 or higher adverse events were observed, mainly hematological. The postoperative mortality rate within 30 days was 4%, and pathological complete response was achieved in 35% of patients. CONCLUSIONS: Intensification of neoadjuvant chemoradiotherapy for patients with potentially resectable esophageal cancer is well tolerated, yielding high pathological complete response rates, but adverse events occurred frequently, and survival compared with conventional neoadjuvant chemoradiotherapy seems similar. Therefore, intensification of neoadjuvant chemoradiotherapy should not be routinely used.

Tolerability of Capecitabine Monotherapy in Metastatic Colorectal Cancer: A Real-World Study.

BACKGROUND: Capecitabine monotherapy is a treatment option for selected patients with metastatic colorectal cancer (mCRC) and is administered to up to 17% of patients. Data are limited with regard to adverse events and dosing practices associated with capecitabine monotherapy in real-world situations. OBJECTIVES: The aim of this study was to provide real-world data on adverse event rates and dose adjustments/discontinuations associated with capecitabine monotherapy in patients with mCRC. METHODS: This retrospective study analyzed data from CRC patients scheduled to receive up to eight planned cycles of capecitabine monotherapy between 2009 and 2013 at a single large community hospital in The Netherlands. Data on adverse events (hand-foot syndrome [HFS], gastrointestinal (GI) events, hematological adverse events, and cardiotoxicity), as well as relative dose intensities (RDIs), dose reductions, and discontinuations, were evaluated. RESULTS: Data from 86 patients (45 females; mean age at the start of treatment, 69 years) were included. A total of 46.5% of patients experienced HFS and 44.2% experienced a GI event at some time during treatment. Hematological events and cardiotoxicity were rare. Most patients (77%) started at below the recommended dose, and patients at the lowest dose also had the lowest median RDIs. Dose reductions and discontinuations occurred in 15-25% of patients who experienced HFS or GI event over the course of eight cycles. CONCLUSIONS: HFS and GI events were very common in patients treated with capecitabine monotherapy in a real-world clinical setting. Most patients started treatment at below the recommended dose, and 15-25% of patients who had HFS or a GI event had a dose reduction or discontinuation.

Use of trastuzumab for HER2-positive metastatic breast cancer in daily practice: a population-based study focusing on the elderly.

The addition of trastuzumab to chemotherapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) prolongs overall survival (OS) in clinical trials. However, treatment patterns and survival in daily practice are unknown. This study aims to compare trastuzumab use and outcome in HER2-positive MBC patients in a population-based cohort with clinical trial cohorts, with a special focus on elderly patients. MBC patients treated with trastuzumab-based chemotherapy in north-east Netherlands between 2005 and 2009 were identified from 23 hospital pharmacies and the Netherlands Cancer Registry. Baseline, treatment, and survival characteristics (Kaplan-Meier analysis) were compared with those found in clinical trials and differences in patients aged less than 65 versus 65 years or more were studied. Of 225 HER2-positive MBC patients (median: 54.8 years), 130 were treated with first-line trastuzumab. In first-line treatment, the median treatment duration was 9 months and the median OS was 30.7 months, which is comparable with the OS of 31.2 months found in a clinical trial with comparable baseline characteristics. In 25 patients aged 65 years or more compared with those aged less than 65 years treated with first-line trastuzumab, patients with a history of early breast cancer had less often been treated with adjuvant chemotherapy (36 vs. 71%; P=0.001). Other baseline characteristics and OS were similar. Patient, treatment, and survival characteristics in a HER2-positive MBC population-based cohort share considerable similarities to those found in clinical trials. The influence of age on trastuzumab treatment was not detected.

Classification and occurrence of clinically significant drug interactions with irinotecan and oxaliplatin in patients with metastatic colorectal cancer.

BACKGROUND: Pharmacokinetic and pharmacodynamic drug interactions with cytotoxic drugs may significantly influence the efficacy and toxicity of chemotherapy. OBJECTIVE: The purpose of this study was to identify drug interactions with irinotecan and oxaliplatin reported in the literature, to assess their clinical significance, and to examine the occurrence of these interactions in patients with metastatic colorectal cancer treated with either irinotecan or oxaliplatin or both. METHODS: To obtain data on drug-drug interactions with irinotecan and oxaliplatin, a literature search of PubMed and EMBASE was conducted using the search terms irinotecan, oxaliplatin, and interactions (English-language studies only published between 1980 and August 2004). The interactions found were subsequently classified for documentation evidence and severity of clinical effect, according to a 5-level classification system of a standard reference text, by a study panel of medical oncologists and clinical pharmacists. Comedication of patients who were treated with irinotecan or oxaliplatin, or both, was then examined to determine the occurrence of clinically significant interactions. RESULTS: Ninety-eight patients (50 women, 48 men;mean age, 60 years) were included in the study. Seventeen interactions with irinotecan were found in the literature, and 11 were classified as clinically significant. Only 1 nonspecific, clinically significant interaction was identified for oxaliplatin. Irinotecan-treated patients received a mean of 8 different comedications and oxaliplatin-treated patients received a mean of 6. Apart from antiemetic and antidiarrheal drugs that were prescribed for treatment-related toxicities, only 1 patient appeared to be exposed to a possible clinically significant interaction (between irinotecan and phenytoin). CONCLUSIONS: Eleven of the 17 interactions with irinotecan that were found in the literature were classified as clinically significant versus 1 clinically significant interaction with oxaliplatin. The occurrence of these interactions in the study patients with metastatic colorectal cancer was low. For medication surveillance purposes, however, the significant interactions should be considered in clinical practice.

Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid.

BACKGROUND: Dose adaptation based on pharmacokinetic parameters has been shown to decrease toxicity of some 5-fluorouracil(5-FU)-based continuous infusion regimens. PATIENTS AND METHODS: In the present study the relationship between 5-FU pharmacokinetics in plasma and in saliva, and toxicity was investigated in 40 patients receiving the combination of 5-FU 425 mg/m2 and folinic acid 20 mg/m2 daily during 5 consecutive days according to the Mayo-regimen. RESULTS: The overall non-hematological and hematological toxicity, as well as mucositis only, were not statistically significant related to the area-under-the-curve in plasma (AUCp) or in saliva (AUCs), nor to the maximum concentration measured in plasma (Cmaxp) or in saliva (Cmaxs). Although statistically significant, the correlation between the AUCp and AUCs was relatively low, implying that salivary pharmacokinetics are not accurately predictive of plasma pharmacokinetics. CONCLUSION: The conclusion of this study is that the application of pharmacokinetic parameters is not appropriate for identification of patients at risk for developing toxicity from treatment with 5-FU according to the Mayo-regimen.