Antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting in palliative first-line treatment of colorectal cancer patients: the Northern Bavarian IVOPAK I Project.

PURPOSE: This study aims to evaluate adherence to guidelines of antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting (CINV) in the palliative first-line treatment of colorectal cancer (CRC) patients in Northern Bavaria. METHODS: We collected detailed information on chemotherapy and supportive drugs in 103 patients within a prospective observational study. The study was conducted to determine quality of care within an interdisciplinary context (first endpoint) and direct costs of palliative treatment for patients with CRC between 2006 and 2010 (second endpoint, Emmert et al. (Eur J Health Econ, 2012) [1]). In this paper, we evaluate adherence to Multinational Association of Supportive Care in Cancer (MASCC) 2006 recommendations for prophylaxis of CINV during the first administration of chemotherapy as well as incidence and grade of CINV within 120 h thereafter. RESULTS: Of the patients studied, 95 patients (92%) received moderately emetogenic (oxaliplatin- and/or irinotecan-containing combined chemotherapy treatment) and eight (8%) received low emetogenic chemotherapy (either 5-fluorouracil (5-FU) or capecitabine monotherapy). Antiemetic prophylaxis could be assessed in 101 out of 103 (98%) of patients. MASCC-recommended antiemetic prophylaxis was prescribed in three patients (3%). Nonadherence was mainly caused by omission of dexamethasone. Nausea and/or vomiting occurred in 18 patients (18%) within a 120-h period. All documented episodes were grade 1 or 2 according to the Common Toxicity Criteria of the National Cancer Institute. None of these patients received the recommended prophylaxis for CINV. In only one patient, antiemetic prophylaxis was intensified during the next chemotherapy application. CONCLUSIONS: In the Integrated Health Care in the Palliative Treatment of Colorectal Carcinoma (IVOPAK) I Project, adherence to the MASCC clinical recommendations was very poor. Extent of CINV in this patient population seems to be underestimated. There is an urgent need to improve clinicians' awareness of this patient-relevant side effect.

Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed by secondary metastatic resection after downsizing.

BACKGROUND: The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV). MATERIAL/METHODS: From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m²) as 1-h infusion followed by 5-FU (2000 mg/m²) combined with FA (500 mg/m²) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57). RESULTS: Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months. CONCLUSIONS: Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).

Efficacy and safety of irinotecan-based chemotherapy for advanced colorectal cancer outside clinical trials: an observational study.

BACKGROUND: This prospective observational study in typical community-based outpatient clinics evaluated the efficacy and toxicity of weekly and biweekly irinotecan-based chemotherapies and their compatibility depending on age. METHODS: 601 patients with advanced or metastatic colorectal cancer receiving first-, second-, or third-line irinotecan-based therapy were regularly analyzed for response and toxicity until the end of therapy. RESULTS: The median age was 65 (28-87) years, approximately one-third of the patients were ≥70 years old. Of all patients, 405 were treated weekly and 68 biweekly. Median overall survival (OS) for first-line therapy was 26.5 months for the <70-year-old patients and 19.4 months for the ≥70-year-old patients. Toxicities were moderate in all groups. Tumor growth control rates (TCR) and median time to progression (TTP) were marginally better for patients <70 years old. Median TTP was 9.9 months in first-line therapy, 9.8 months after adjuvant therapy, 7.7 months in second-line, and 6.4 months in third-line therapy. CONCLUSIONS: Toxicity and response data from this observational study clearly confirm the positive results from previous clinical studies and show a slight ad-vantage in efficacy for the <70-year-old patients.

Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer.

BACKGROUND: Combination therapy of irinotecan, folinic acid (FA) and 5-fluorouracil (5-FU) has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases. METHODS: A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2), L-FA (200 mg/m2) and 5-FU bolus (400 mg/m2) on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2). One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients. RESULTS: The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%). Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%), nausea/vomiting (12%), leucopenia (3%), neutropenia (9%) and mucositis (3%). The overall response rate was 31% (4 CR and 7 PR), with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively. CONCLUSIONS: The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant protocols.