Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma

Scheithauer, Werner; Kornek, Gabriela; Ulrich‐Pur, Herbert; Penz, Melitta; Raderer, Markus; Skalický, T; Haider, Karin; Kwasny, Werner; Depisch, D.

doi:10.1002/1097-0142(20010401)91:7<1264::aid-cncr1127>3.0.co;2-x

Cited by 48 publications

(26 citation statements)

References 18 publications

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“…Subsequent phase II studies have attempted to define the activity of raltitrexed in combination with other agents in colorectal cancer. One of the most active doublets is an oxaliplatin combination, and in 6 separate studies (Table 14 [219][220][221][222][223][224]), response rates of between 43 and 62% were obtained in a frontline setting. Activity drops to between 16 and 33% in previously treated patients (Table 15 […”

Section: Raltitrexedmentioning

confidence: 80%

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

2006

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Section: Raltitrexedmentioning

confidence: 80%

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

2006

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“…These symptoms occur frequently in end-stage colorectal cancer patients. [25][26][27] Mutations in the p53 gene occur in approximately 50% of malignancies and usually result in overexpression in the malignant cells only. 3 The combination of increased steady-state levels and predominant expression by malignant cells provided an opportunity for a p53-specific immunotherapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients

et al. 2003

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Overexpression of p53 occurs in more than 50% of colorectal cancers. Therefore, p53 represents an attractive target antigen for immunotherapy. We assessed the safety of a canarypox virus encoding the human wild-type p53 gene given intravenously to endstage colorectal cancer patients in a three-step dose escalation study aimed at inducing p53 immune responses. Patients with metastatic disease of p53-overexpressing colorectal cancers were vaccinated three times at 3-week intervals, each time with 10 6.5 CCID 50 (CCID 50 ¼ cell culture infectious dose 50%; group 1, n ¼ 5), 10 7.0 CCID 50 (group 2, n ¼ 5) or 10 7.5 CCID 50 (group 3, n ¼ 6). Vital signs and the occurrence of adverse events were monitored and blood was analyzed for biochemical and hematological parameters as well as signs of auto-immune safety. In all, 16 patients were enrolled and 15 patients completed three vaccinations. No anaphylactic reaction or unwanted auto-immune reactions were observed. A total of 16 serious adverse events (SAEs) occurred: 10 in group 1, three in group 2 and three in group 3. All SAEs were tumor-related complications. There was no difference in the frequency of adverse events between the three groups, except for fever. Fever was the only vaccination-related adverse event consistently observed and was most frequent and outspoken in the group 3 patients. The majority was a grade 1 or 2 fever (93%) and grade 3 fever (7%) was observed in three patients of group 3. Some patients showed humoral and cellular responses against p53, following vaccinations. After having completed his initial treatment cycle, one patient (group 2) received a second treatment cycle of three doses of 10 7.5 CCID 50 and subsequently showed stable disease. All other patients showed progressive disease. We conclude that ALVAC-p53 can be administered intravenously to colorectal cancer patients without serious toxicity or pathological autoimmunity and can induce immune responses against p53.

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“…In the second trial, the same dose regimen was administered to patients failing prior fluoropyrimidine/LV-based chemotherapy (Scheithauer et al, 2001b). The third trial was a randomised multicentre phase II trial of oxaliplatin plus irinotecan vs raltitrexed as first-line treatment with a crossover design upon progression (Scheithauer et al, 2001c): patients randomised to the combination arm, were treated with oxaliplatin 85 mg m À2 and irinotecan 175 mg m À2 every 2 weeks. Patients randomised to the raltitrexed-arm received a dose of 3 mg m À2 given on day 1 every 3 weeks.…”

Section: Chemotherapymentioning

confidence: 99%

Side effects during chemotherapy predict tumour response in advanced colorectal cancer

et al. 2005

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To investigate whether a relationship between chemotherapy-associated adverse events and treatment efficacy exists, we have analysed the toxicity, objective response and survival data of 303 patients with advanced colorectal cancer. Patients were divided into two groups: the first with beneficial effect (I, n ¼ 245), and the second with progressive disease (II, n ¼ 58). Differences in terms of incidence rates, type and severity of adverse events were analysed with univariate and multivariate models. The median number of side effects in group I was 6 vs 4 in group II (OR ¼ 1.342; P ¼ 0.0001). An inverse correlation between disease control and treatment tolerance was confirmed when side effects were analysed according to severity and type of treatment-associated toxicities (haematological: P ¼ 0.0005 vs nonhaematological P ¼ 0.0001). When median survival was analysed according to the number of adverse events, it was 10 (95% CI, 3 -7), 16 (14 -18), and 18 (16 -20) months in case of 0 -1, 2 -5, and X6 adverse events, respectively (P ¼ 0.01). In conclusion, the results of this analysis suggest that occurrence of side effects during chemotherapy in advanced colorectal cancer is an independent and reliable prognostic indicator for response and survival.

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Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma

Cited by 48 publications

References 18 publications

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients

Side effects during chemotherapy predict tumour response in advanced colorectal cancer

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