[show abstract][hide abstract] ABSTRACT: : The multinational MABEL study of 1147 patients with metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen confirmed in a community practice setting the efficacy and safety of cetuximab combined with irinotecan.
: This report describes a post hoc analysis of the influence of prophylactic premedication on the incidence of infusion-related reactions (IRRs) in the MABEL study. The analysis was focused on the subpopulation of patients premedicated with antihistamines either with (n = 700) or without (n = 422) corticosteroids. Stepwise Cox regression modeling was used to examine the explanatory value of the type of premedication on progression-free survival (PFS) and overall survival (OS) times.
: The incidence of IRRs was lower in the group of patients who received antihistamine plus corticosteroid (9.6%) compared with those who received antihistamine alone (25.6%). A similar trend was seen for grade 3 or 4 IRRs (1.0% vs 4.7%, respectively). The 12-week PFS rates (61% vs 60%), median PFS (16.1 vs 13.1 weeks) and OS (9.2 vs 9.0 months) times for patients who received, respectively, antihistamines with and without corticosteroids were similar. Cox regression modeling did not identify any impact of type of premedication used (antihistamine with or without corticosteroids) on the efficacy of treatment in relation to PFS or OS.
: Prophylactically premedicating mCRC patients with both antihistamine and a corticosteroid appeared to reduce the frequency of cetuximab-associated IRRs. Given that this was a post hoc analysis, caution must be exercised in the interpretation of these data, which require formal confirmation in a randomized study. Cancer 2010. (c) 2010 American Cancer Society.
Cancer 02/2010; 116(7):1827-37. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: This large, multinational study aimed to confirm in a community practice setting the efficacy and safety of cetuximab plus irinotecan in patients with epidermal growth factor-expressing metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen.
The primary objective was to determine the progression-free survival (PFS) rate at 12 weeks. The initial cetuximab dose was 400 mg/m(2) and was followed weekly by 250 mg/m(2); irinotecan (according to prestudy regimen) was given weekly (125 mg/m(2) weekly for 4 of 6 weeks), every 2 weeks (180 mg/m(2) each), or every 3 weeks (350 mg/m(2) each).
The intention-to-treat/safety population comprised 1,147 treated patients who received irinotecan weekly (n = 93); every 2 weeks (n = 670); every 3 weeks (n = 356); or another dose (n = 28). The PFS rate at 12 weeks was 61%, and the median survival was 9.2 months. Treatment was generally well tolerated. The most common treatment-related grades 3 to 4 adverse events were diarrhea (19%), neutropenia (10%), rash (7%), and asthenia (6%). The rate of grades 3 to 4 infusion-related reactions (IRRs; composite adverse event category) was 1% for patients who received both antihistamine and corticosteroid premedication. CONCLUSION Tolerability (except IRR incidence), PFS rate, and overall survival rate were in line with previous results. At 1%, the rate of IRRs in patients who received prophylactic premedication with both antihistamine and corticosteroid is lower than previously reported. MABEL clearly confirms in a community practice setting the efficacy and safety of cetuximab plus irinotecan in the treatment of mCRC.
Journal of Clinical Oncology 11/2008; 26(33):5335-43. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Options for first-line chemotherapy in patients with metastatic colorectal carcinoma have broadened considerably with the introduction of irinotecan and oxaliplatin. Furthermore, the oral fluoropyrimidine capecitabine has demonstrated efficacy in Phase III trials and recently was approved for first-line treatment in Europe and the United States. Capecitabine yielded similar median times to disease progression and median survival rates compared with bolus 5-fluorouracil (5-FU)/leucovorin (LV) (Mayo Clinic/North Central Cancer Treatment Group regimen), with superior and similar response rates, respectively. However, its role as a first-line, single-agent substitute for intermittent infusional 5-FU/LV remains to be defined. The addition of irinotecan or oxaliplatin to 5-FU/LV resulted in improved response rates and progression-free survival in large, randomized trials; moreover, irinotecan-containing regimens resulted in improved overall survival. Prevalent regimens of irinotecan/5-FU/LV and oxaliplatin/5-FU/LV have been compared in two randomized Phase III trials. One study demonstrated the statistical superiority of oxaliplatin/infusional 5-FU/LV over irinotecan/bolus 5-FU/LV in terms of response, time to disease progression, and median survival; however, those advantages may have been attributable to infusional administration or to major differences in second-line therapy. A randomized Phase III study comparing irinotecan and oxaliplatin in combination with the same infusional 5-FU/LV regimens and crossover in case of disease progression showed equivalent efficacy for both schedules in the first-line setting, but the irinotecan combination proved beneficial in terms of safety. New molecular targeted agents, such as angiogenesis-modulating compounds (e.g., bevacizumab) and epidermal growth factor receptor inhibitors (e.g., cetuximab), are under clinical investigation. This review updates current systemic frontline treatments and future perspectives for patients with advanced colorectal carcinoma.
Cancer 05/2004; 100(8):1558-77. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the response rate and the tolerance of irinotecan as first-line therapy, 40 patients with metastatic gastric cancer received irinotecan 350 mg m(-2) every 3 weeks administered as a 30 min infusion. Among the 35 patients evaluable for response, two complete and five partial responses were recorded (response rate: 20.0% (95% CI:8.4-36.9%)). In total, 16 patients achieved stable disease and 12 progressive disease. In all, 66 percent of the patients benefited from tumour growth control. The median time to progression was 3.0 months (95% CI: 2.3-4.4%). The median overall survival was 7.1 months (95% CI: 5.2-9.0%). The probability of being alive at 6 months and 9 months was 61.0 and 32.4%, respectively. The median number of cycles per patient was 3 (range 1-14), and the relative dose intensity was 0.98. The most common grade 3-4 toxicities by patients were diarrhoea 20%, asthenia 10%, nausea 7.5%, vomiting 5.0%, abdominal pain 5%, neutropenia 38.5%, leucopenia 28.2%, anaemia 12.8% and thrombocytopenia 5.1%. Febrile neutropenia occurred in 12.5% of patients. These findings indicate that irinotecan is active and well tolerated in patients with metastatic gastric adenocarcinoma and warrants further evaluation in this clinical setting.
British Journal of Cancer 10/2003; 89(6):997-1001. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Im Verlauf der letzten drei Jahrzehnte hat sich die allgemeine Einstellung bezüglich des klinischen Wertes der Chemotherapie
des Magenkarzinoms wesentlich geändert. Hierzu hat speziell die Entwicklung moderner Chemotherapiekonzepte, sogenannte “second”
und “third generation” Chemotherapieprotokolle beigetragen. Darüber hinaus konnte in randomisierten Studien gezeigt werden,
dass eine Chemotherapie im Vergleich zu einer alleinigen supportiven Therapie (best supportive care) nicht nur die Überlebenszeiten
signifikant verbessert sondern auch die Lebensqualität positiv beeinflusst (Tabelle 1) [1, 2, 3, 4]. Mittlerweile wird die
Chemotherapie sowohl in palliativer Intention bei Patienten mit metastasierter Erkrankung eingesetzt als auch zunehmend im
perioperativen Bereich. Die Chemotherapie des fortgeschrittenen Magenkarzinoms wird heutzutage als eine international akzeptierte
Der Onkologe 05/2001; 7(6):632-648. · 0.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Local irresectable carcinoma of the pancreas was diagnosed by explorative laparotomy of a 62-years old patient. At this stage (T3 N1 M0), a curative surgical therapy was not possible. The prognosis in these cases is bad. Medium survival time is less than half a year. In order to improve prognosis a combined radiochemotherapy has been applied. The total tumor dose of 44.8 Gy was applied in 2 daily fractions of 1.6 Gy. On the first 3 days of radiotherapy 600 mg/m2 5-FU and 300 mg/m2 folinic acid were given i.v.. Chemotherapy was repeated each 28 days. After 45 months of observation and application of 20 courses chemotherapy no local or systemical progress can be proven in this patient. His health status is good. A combined radio-chemotherapy improves prognosis in locally irresectable carcinoma of the pancreas. In particular cases survival time is surprisingly long.
Zentralblatt für Chirurgie 01/1998; 123(5):579-82. · 0.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma.
The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m2 i.v. 15-minute infusion followed by methotrexate 200 mg/m2 i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m2 i.v. push on day 2. Folinic acid was given at 15 mg/m2 p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks.
Thirty patients with advanced chemotherapynaive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27-72); median PS 1 (0-2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients.
Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.
Annals of Oncology 10/1997; 8(9):917-8. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: In spite of improved surgical techniques and the use of multiple modality treatment schemes the local recurrence rate of colorectal carcinomas could not be successfully reduced up to now. Besides surgical treatment of local recurrences in some cases radiation therapy may be indicated.
In the Department of Radiotherapy of the University of Münster 37 patients with recurrent rectal carcinoma were treated between the end of 1985 and September 1992 either with fast neutrons alone or with a combined photon-neutron therapy. Eighteen patients received radiotherapy with fast neutrons (14 MeV d,T) alone; the tumor dose was between 10 and 15 Gy neutrons. Nineteen patients were irradiated with a mixed-beam schedule consisting of 30 to 45 Gy photons (X 10 MV) and neutron doses ranging from 5 to 10 Gy.
In 30 patients a good or complete pain relief could be observed immediately after the last irradiation. Sixteen out of 37 patients had local tumor regrowth during the follow-up period. The median survival for all 37 patients was 15.9 months. The probability for survival was 86% after 6 months and 61% after 12 months (Kaplan-Meier). The side effects were slight to moderate (EORTC/RTOG I-II).
This therapy showed good results concerning a fast and effective pain relief. Additionally the results seem to show a good effect concerning local control and overall survival in this negatively selected patients.
Strahlentherapie und Onkologie 07/1997; 173(6):316-22. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Between July 1990 and September 1993, 32 patients with locally advanced irresectable adenocarcinoma of the pancreas, histologically proven by laparotomy, were involved in our study. Patients were treated with hyperfractionated, accelerated radiotherapy and simultaneous application of 5-fluorouracil and folinic acid. Chemotherapy was given on days 1,2 and 3. Determination of the target volume for radiotherapy was carried out by computerized axial tomography. The total tumour dose of 44.8 Gy was applied relative to the 90% isodose in two daily fractions of 1.6 Gy, resulting in ten fractions per week. On the first three days of radiotherapy, 600 mg m-3 of 5-fluorouracil and 300 mg m-3 of folinic acid were given i.v. According to response, chemotherapy was repeated in 4-week intervals. The median survival time for all patients was 12.7 months, compared with 3-7 months after palliative surgery (historical control). The median progression-free interval was 6.6 months. Toxicity and therapy-induced morbidity were recorded according to WHO criteria. Nausea and vomiting of WHO grade I and II occurred in 72.1% and of grade III and IV in 27.9% of the patients. WHO grade I and II diarrhoea was seen in 11 patients. The overall incidence of leucopenia and thrombocytopenia was 37.4%; severe side-effects (WHO III-IV) occurred in 9.3% of all patients. One patient experienced a severe mucositis (WHO III). This combined modality treatment consisting of accelerated hyperfractionated radiotherapy and chemotherapy turned out to be feasible for patients with locally advanced, irresectable pancreatic cancer. The therapy could be applied in a short period of time, approximately half the time used in conventional therapy schemes.
British Journal of Cancer 02/1997; 75(4):597-601. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: We undertook a multicenter phase II trial of 5-fluorouracil (5FU) + 1-leucovorin (1-LV) in previously untreated patients with metastatic colorectal cancer to determine the response rate, response duration, time to progression, survival, and toxicity. Patients were treated with i.v. 5FU 370 mg/m2/day and 1-LV 100 mg/m2/day x 5 every 28 days. Toxicity and response were determined by WHO criteria. One hundred and twenty-six patients were entered, and 119 patients were eligible and evaluable. Eighty-eight patients had colon cancer and 37 had rectal cancer. The male:female ratio was 58:68. The mean age was 62.2 years. ECOG performance status distribution was 0 (39.7%), 1 (46%), and 2 (11.9%). The median number of courses of therapy administered was 4.5. Severe- or life-threatening stomatitis or diarrhea, nausea, and granulocytopenia occurred in 17.6, 23.2, 17.6, and 15.9% of patients, respectively. The response rate was 22/119 [18.5%; 95% confidence interval (CI) of 12.0-26.6]. Median response duration was 188 days (95% CI of 111-248 days). Median survival was 379 days (95% confidence interval of 289-452 days). These results indicate that when 1-LV is combined with 5FU, toxicity is similar in pattern and severity to that of the d,1 racemic mixture. The overall efficacy of 1-LV + 5FU is comparable to a recent metaanalysis.
American Journal of Clinical Oncology 03/1996; 19(1):26-31. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Based on preclinical data and the promising results being achieved with infusional 5-FU in colorectal and breast cancer, we investigated a weekly schedule of a 24-hour infusion of 5-FU plus folinic acid (HD-FU/FA) in patients failing to first-line chemotherapy and HD-FU/FA plus cisplatin (C) or plus cisplatin/epidoxorubicin (C/E) in chemo-naive patients with advanced gastric cancer. In all three trials the results achieved with the tested chemotherapy regimens indicated high activity and good tolerability. All three protocols were administered as outpatient treatment. With HD-FU/FA and overall response rate of 24% and a median survival time of 5 months was observed in 17 patients refractory to or relapsing after first-line chemotherapy. HD-FU/FA/C induced an overall response rate of 66% and a median survival time of 13 months. Of note was the high activity of this regimen in patients with malignant ascites. HD-FU/FA/C/E also proved to be an interesting regimen similar active as HD-FU/FA/C but it was subjectively less well tolerated. In patients with locally advanced disease the response rate was 90% (10/11), and in patients with distant metastases 50% (8/16).
The Journal of infusional chemotherapy 02/1996; 6(3):123-6.
[show abstract][hide abstract] ABSTRACT: 38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.
European Journal of Cancer 02/1994; 30A(3):325-8. · 5.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: 38 patients with advanced oesophageal carcinoma were treated with intravenous (iv) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22–28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% () including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation ± 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leucocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.
European Journal of Cancer - EUR J CANCER. 01/1994; 30(3):325-328.