Raltitrexed in the management of metastatic colorectal cancer: The COMET study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 677-677
Author(s):  
Jérôme Desramé ◽  
Louis-Marie Dourthe ◽  
Philippe Debourdeau ◽  
Dominique Mille ◽  
Pascal Artru ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Combination Therapy ◽  
Treatment Failure ◽  
Folinic Acid ◽  
Disease Progression ◽  
Cardiac Toxicity ◽  
Tumour Progression ◽  
Single Agent ◽  
Patient Consent

677 Background: Raltitrexed, indicated for palliative treatment of advanced colorectal cancer (CRC), may be useful for patients (pts) with cardiovascular (CV) risk factors, or cardiotoxicity/disease progression with prior chemotherapy (CT). The COMET study, conducted in France, described the characteristics of pts with metastatic CRC (mCRC) treated with raltitrexed, focusing on pts with cardiotoxicity or disease progression with prior 5-fluorouracil (5FU)/folinic acid. Methods: A national, multicentred, cross-sectional, non-interventional study to describe the profiles of pts with mCRC treated with raltitrexed. Pts (≥18 years) with mCRC, treated with raltitrexed as a single agent or in combination therapy, were included. Following patient consent, retrospective data were recorded during a single inclusion visit based on pt medical files; during the study, data were recorded prospectively. Results: 414 pts with mCRC were analysed; 84.8% had ≥1 prior CT, 60.9% had CV risk factors and 35.2% had CV history (angina: 11.8%; myocardial infarction: 11.8%). Overall, 79.5% of pts had received a prior 5FU-based CT. Reasons for switching to raltitrexed included short 15-min infusion duration (34.8%), treatment failure (49.8%) and acute cardiotoxicity with 5FU (8.9%). After switching, 57.2% of pts received raltitrexed as combination therapy. Mean initial dosage of raltitrexed was 2.6±0.6 mg/m2. Of those who had CV risk factors (n=73) or CV history (n=67), 69.0% and 72.7% received raltitrexed after CV toxicity, respectively. Of the pts treated with second-line raltitrexed and assessed with prior acute CV events (45/414), 88.9% (40/45) had no cardiac toxicity during treatment with raltitrexed. Of those (n=206) receiving raltitrexed due to treatment failure, 62.7% had received 5FU/folinic acid during their last CT. Of the pts assessed for tumour response (183/206), tumour progression was controlled with raltitrexed in 25.7% of cases (stable disease: 18.0%; partial response: 7.7%; progressive disease: 56.3%). Conclusions: Raltitrexed appears to be effective in heavily pretreated pts with mCRC and tumour progression after 5FU therapy and could be a safe therapeutic alternative to 5FU for pts with mCRC and prior cardiac toxicity.

Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy

2007 ◽  
Vol 25 (16) ◽  
pp. 2171-2177 ◽  
Author(s):  
Jan B. Vermorken ◽  
José Trigo ◽  
Ricardo Hitt ◽  
Piotr Koralewski ◽  
Eduardo Diaz-Rubio ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Combination Therapy ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Disease Progression ◽  
Response Rate ◽  
Single Agent ◽  
Open Label ◽  
Metastatic Squamous Cell Carcinoma

PurposeTo evaluate the efficacy and safety of the epidermal growth factor receptor–directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy.Patients and MethodsAn open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2followed by subsequent weekly doses of 250 mg/m2) for ≥ 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase). From June 2001 to December 2002, 103 patients were enrolled and treated with cetuximab, 53 of whom subsequently received combination therapy.ResultsIn the single-agent phase, response rate was 13%, disease control rate (complete response/partial response/stable disease) was 46%, and median time to progression (TTP) was 70 days. During the combination-therapy phase, the objective response rate was zero, disease control rate was 26%, and TTP was 50 days. Median overall survival was 178 days. Treatment was well tolerated. The most common cetuximab-related adverse events in the single-agent phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or 2). There was one treatment-related death due to an infusion-related reaction.ConclusionSingle-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.

Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid.

1986 ◽  
Vol 4 (5) ◽  
pp. 685-696 ◽  
Author(s):  
D Machover ◽  
E Goldschmidt ◽  
P Chollet ◽  
G Metzger ◽  
J Zittoun ◽  
...  
Keyword(s):  
Survival Time ◽  
Folinic Acid ◽  
Disease Progression ◽  
Median Time ◽  
Gastric Adenocarcinoma ◽  
Median Survival ◽  
Median Survival Time ◽  
Single Agent ◽  
High Dose ◽  
Gastric Adenocarcinomas

We report the results of an expanded trial of 5-fluorouracil (5-FU) combined with high-dose folinic acid for treatment of patients with advanced colorectal or advanced gastric adenocarcinoma. In each treatment course, the patients received both 5-FU (340 to 400 mg/m2/d by intravenous (IV) infusion for a period of 15 minutes) and folinic acid (200 mg/m2/d by IV bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete and partial response rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to 5-FU attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates greater than 10(-5) mol/L were achieved after a rapid single IV injection of 200 mg/m2 of folinic acid. Comparisons of our results with those reported in previous studies on 5-FU administered as a single agent suggest that, in advanced colorectal and gastric adenocarcinoma, folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly. Furthermore, some colorectal tumors that were previously resistant to 5-FU become sensitive to this drug. The survival of the patients who responded to therapy was markedly improved over that observed in reported series of untreated patients with advanced colorectal and gastric adenocarcinomas.

Maintenance treatment with cetuximab in a series of patients treated with standard chemotherapy and cetuximab in metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 624-624
Author(s):  
G. Quintero-Aldana ◽  
S. Varela ◽  
B. Campos ◽  
S. Vazquez-Estevez ◽  
O. Maseda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Standard Chemotherapy ◽  
Cutaneous Toxicity

624 Background: New strategies are needed to improve outcomes and reduced toxicities of currently treatments for patients with advanced colorectal cancer. Nowadays maintaining treatment until disease progression is the standard option for these patients. Cetuximab is a recombinant humanized monoclonal antibody that neutralizes epidermal growth factor receptor and it has shown benefit not only in combination with standard chemotherapy in first- and second-line treatment or as a single agent in progression to standard chemotherapy in KRAS wild-type metastatic colorectal cancer (mCRC). Methods: This data describes patients who received standard chemotherapy with cetuximab every two weeks. For patients with response or stable disease, cetuximab was continued until disease progression or unacceptable toxicity. Results: Twelve patients are reported, nine were male (75%). The median age was 62 years (range, 46 to 78 years). All patients had stage IV, and liver was the most common location (75%). The majority of patients (75%) received FOLFOX VI as a first-line treatment in combination with cetuximab; only two patients were treated with FOLFIRI. Cetuximab was maintained after the first line of treatment in the 75% of patients. The median of cycles of chemotherapy and cetuximab was 12. Best response achieved in this setting was complete response (58.3%, 7/12). Median of monotherapy with cetuximab treatment was 7.5 cycles (range 3 to 12). At the moment of this analysis seven of twelve patients continued with the maintenance. In the rest of patients the treatment was followed until progression (33%, 3/12). No grade 3-4 toxicities were seen during maintenance cetuximab. The most common adverse effect during maintenance was cutaneous toxicity but the majority of patients had minor toxicity (50% grade 1). Conclusions: Cetuximab has significant antitumor activity not only as a single agent or in combination with standard chemotherapy but may also when it is used as maintenance therapy after a complete or partial response to first or second line based chemotherapy in mCRC. Maintenance cetuximab is feasible, safe, and worthy of future study in advanced colorectal cancer. No significant financial relationships to disclose.

scholarly journals Proteinemia as a Prognostic Factor in Colorectal Cancers beyond Surgery and Chemotherapy

2021 ◽  
Author(s):  
Linah Waleed Khalid Al-Hishma
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Folinic Acid ◽  
Surgical Procedures ◽  
Protein Concentration ◽  
Single Agent ◽  
Nutritional Deficiencies ◽  
Female Ratio ◽  
The Mean ◽  
Cancer Multiple

Abstract Background Globally, 1,096,601, 704,376, and 48,541 new colon, rectum, and anus cancer cases were recorded in 2018, respectively. Besides, 551,269, 310,394 and 19,129 cases of colon, rectum, and anus cancer deaths occurred in the same year. As a result, these cancers ranked in the third level of cancer incidence, and in the second level of cancer mortality. As it is known, all cancer patients are subjected to cancer-induced and therapy-induced nutritional deficiencies (mainly of proteins and calories). The present study aimed to assess proteins level in colorectal cancer (CRC) patients who underwent surgery and chemotherapy. Methods A combined retrospective and prospective study was performed. The present study enrolled 100 CRC patients with their data on surgical procedures and chemotherapy management. Assessments of the studied samples were conducted as a baseline before receiving chemotherapy and preoperatively as P0, while the period after that was termed as P1. The serum samples were collected to measure protein concentration. Total Protein Kit, Micro was used. Results The mean age of the patients was 50.7 ± 12.88 years old. Only 8% had a positive CRC family history. Rectosigmoid cancer represented the most frequent site, figured in 41% of the cases, followed by rectum cancer. Multiple sites of CRC metastasis were recorded in 15% of the patients. All patients received chemoradiation. Folinic acid (leucovorin), 5-FU, and oxaliplatin (FOLFOX) was the most used regimen, administered in 40% of the patients. Oxaliplatin and capecitabine (also called Xeloda) (XELOX) were administered in 14% of the patients. Folinic acid (leucovorin), 5-FU, oxaliplatin, and irinotecan (FOLFOXIRI) were administered in 16% of the patients. Single-agent oxaliplatin or carboplatin were administered in 6% of the patients, each. 5-FU plus leucovorin was administered to12% of the patients. Three patients received irinotecan, and oxaliplatin (IROX). One patient received folinic acid (leucovorin), 5-FU and irinotecan (FOLFIRI). Also, Gemzar was administered to two patients only. A total of 80% of the patients underwent several surgical procedures. Anterior perineal resection (APR) and total mesorectal excision (TME) were the most common two surgeries, performed in 20 and in 30% of the patients, respectively. In P0 status, 44% of the patients suffered from low protein levels, and 13% of the patients were within the normal level. These findings were statistically different (p = 0.03). After CRC management (i.e., P1 status), 70% of the patients had protein deficiency. These results have strong significant differences (p = 0.000). The mean of protein concentration declined gradually after management, from 8.82 ± 0.9 μg/L to 6.21 ± 0.78 μg/L, with a strong association between a reduction in proteins levels towards deficiency and surgical procedures and chemotherapy protocols (p = 0.000). Conclusion The incidence of CRC is increasing annually, and the chance of being diagnosed with this type of cancer has risen in recent years. In the present study, the male to female ratio was 1:1.5, and the 5th decade of life was the most common age for the diagnosis of CRC. A negative family history and bowel inflammatory diseases (IBD) history did not exclude people from exposure to the incidence of CRC. Colorectal cancer with localized and moderately differentiated adenocarcinoma were the most common types in the present work. Tumor distance from the anal verge seems to be very important and plays a significant role in the choosing of surgical intervention types and chemoradiation protocols. Colorectal cancer acts as a complex condition and, in addition to its management, nutritional state influences it in different mechanisms. Most patients suffered from hypoproteinemia after surgery and chemoradiation. As a result, alteration in the treatment outcomes, delaying in wound healing, and an increase in postoperative complications may occur.

scholarly journals Single-agent therapy with sorafenib or 5-FU is equally effective in human colorectal cancer xenograft—no benefit of combination therapy

2012 ◽  
Vol 28 (3) ◽  
pp. 385-398 ◽  
Author(s):  
Thomas C. Wehler ◽  
Swaantje Hamdi ◽  
Annett Maderer ◽  
Claudine Graf ◽  
Ines Gockel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Single Agent ◽  
Human Colorectal Cancer ◽  
Single Agent Therapy

A New Strategy Of MDS Treatment With Azacitidine (AZA): Induction With AZA Combined With Low Dose AraC Followed By Maintenance Therapy With AZA

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1536-1536
Author(s):  
Manabu Hirai ◽  
Takahiko Nakane ◽  
Atsushi Inoue ◽  
Mitsuharu Hashimura ◽  
Mizuki Aimoto ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Maintenance Therapy ◽  
Disease Progression ◽  
Low Dose ◽  
De Novo ◽  
Single Agent ◽  
Treated Group ◽  
Significant Difference ◽  
De Novo Aml ◽  
Very High

Abstract Introduction Azacitidine (AZA) is a promising agent for higher risk myelodysplastic syndrome (MDS), but it does not prevent disease progression as a single agent in most cases of AML. MDS is a heterogeneous disease not only pathologically but also clinically. Some cases have progressive clinical stages and disease-related symptoms (fever, edema and effusion), so called aggressive MDS (aMDS). Since some aMDS cases failed single agent AZA treatment, we considered combination chemotherapy with AZA for aMDS. Here we report the use of low dose of AraC followed by AZA for aggressive MDS in a pilot study. Method We evaluated eligible 37 MDS, CMML, overt AML and de novo AML patients from March, 2011 to June, 2013. All MDS and CMML patients had disease-related symptoms or disease progression in the previous 3 months. Twenty-two patients (median age 73 years, range 55-87) were treated with single agent AZA (sAZA) 75 mg/m2/day i.v. 1∼5, 8, 9 days every four weeks. For low dose AraC combination therapy, AraC 10mg/m2xtwice/day s.c. for 1∼5 days and Aclarubicin Hydrochloride (Aclacinon) 20 mg/m2/day i.v. for 1, 2days (CA therapy) was followed by AZA 75 mg/m2/day iv for 7 days (8∼12, 15, 16). Fifteen patients (median age 74 years, range 62∼85) received sAZA after 1 cycle of CA followed by AZA (CA-AZA). Responses were scored according to IWG 2006 criteria for MDS. Results Diagnosis was RCMD n=3, RAEB1 n=4, RAEB2 n=10, CMML n=1, overt AML n=3, de novo AML n=1 for sAZA-treated group and RCMD n=1, RAEB1 n=2, RAEB2 n=6, CMML n=2, overt AML n=4 for CA-AZA-treated group. IPSS-R risk category was intermediate n=6, high n=2, very high n=8 for sAZA-treated group and intermediate n=1, high n=1, very high n=7 for CA-AZA-treated group. Overall response rate was 27.2% and 80% for sAZA- and CA-AZA-treated groups, respectively. 50% of progressive disease and 9% (n=2) of failure (death) were observed in sAZA group at 1 to 3 courses of AZA. One year overall survival (1yOS) was 38.1% and 90.9% in sAZA- and CA-AZA-treated groups, respectively, without significant difference (P=0.11). In overt AML, CA-AZA treatment resulted in a significant difference in 1yOS (0% vs. 100%, P=0.02). In the higher risk groups (High, Very high and overt AML) and the poor and very poor karyotype groups, CA-AZA treatment showed a trend towards improved 1yOS (P=0.07, P=0.11) compared with sAZA. Adverse events were similar between two treatment groups. Conclusions For aMDS, sAZA therapy was not sufficient to control disease progression. To suppress disease progression and to improve the efficacy of AZA, we used CA prior to AZA maintenance therapy. In one case with overt AML and in two cases of aggressive type CMML, CA with AZA maintenance successfully prevented disease progression for almost two years. These three cases are now being treated every two or three months with sAZA as maintenance therapy. AZA combination therapy with AraC have been examined in in vitro and in vivo studies (R.L. Momparler Cancer Res. 1975;35, G.L. Neil Cancer Res. 1976;36). Our low dose and short term chemotherapy (CA) was safely and effectively combined with AZA for older aMDS patients. We are planning a clinical study to further evaluate CA-AZA therapy in a larger cohort of patients. Disclosures: Hirai: NIPPON SHINYAKU CO.,LTD: Speakers Bureau. Hino:NIPPON SHINYAKU CO.,LTD: Research Funding.

Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer.

1995 ◽  
Vol 13 (10) ◽  
pp. 2567-2574 ◽  
Author(s):  
S Jones ◽  
E Winer ◽  
C Vogel ◽  
L Laufman ◽  
L Hutchins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Failure ◽  
Advanced Breast Cancer ◽  
Randomized Trial ◽  
Disease Progression ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Breast ◽  
Time To Treatment ◽  
Time To Treatment Failure

PURPOSE This prospective multicenter randomized trial was performed to compare the effectiveness and safety of intravenous (i.v.) vinorelbine tartrate (Navelbine [NVB]; Burroughs Wellcome Co, Research Triangle Park, NC) with i.v. melphalan (Alkeran [ALK]; Burroughs Wellcome Co) in a heavily pretreated population of patients with anthracycline-refractory advanced breast cancer (ABC). Efficacy end points included time to disease progression (TDP), time to treatment failure (TTF), survival, tumor response rates, and quality of life (QL) and relief of cancer-related symptoms. PATIENTS AND METHODS Between August 24, 1990, and December 1, 1992, 183 patients were randomized (2:1) to treatment with NVB (30 mg/m2 weekly) or ALK (25 mg/m2 every 4 weeks) i.v. Patients were stratified by measurable or nonmeasurable-assessable disease and by treatment center. RESULTS Time to disease progression was significantly longer with NVB than with ALK, with a median 12 weeks versus 8 weeks, respectively (P < .001). NVB patients also had significantly longer time to treatment failure than ALK patients, with a median 12 weeks versus 8 weeks, respectively (P < .001). The effect of NVB on survival was also statistically significant (P = .034): 1-year survival rates were 35.7% with NVB and 21.7% with ALK and the median survival rate was 35 weeks and 31 weeks, respectively. In total, 46.5% of NVB patients and 28.2% of ALK patients achieved an objective response or stabilization of disease (P = .06). No intergroup differences were noted in patient-assessed QL and cancer-related symptoms. The most common toxicities were hematologic, including granulocytopenia with NVB and thrombocytopenia and granulocytopenia with ALK. Both drugs were generally well tolerated, and no septic deaths were reported. CONCLUSION This randomized trial demonstrates a survival benefit in anthracycline-refractory ABC. NVB was well tolerated and demonstrated activity superior to ALK in anthracycline-refractory ABC, without compromising QL. Based on activity of single-agent NVB in this difficult-to-treat patient population, investigations of NVB in combination with other anticancer drugs are warranted.

Safety and Toxicity Analysis of Oxaliplatin Combined With Fluorouracil or as a Single Agent in Patients With Previously Treated Advanced Colorectal Cancer

2003 ◽  
Vol 21 (15) ◽  
pp. 2904-2911 ◽  
Author(s):  
Ramesh K. Ramanathan ◽  
Jeffery W. Clark ◽  
Nancy E. Kemeny ◽  
Heinz-Josef Lenz ◽  
Kim O. Gococo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Failure ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Dose Intensity ◽  
The United States ◽  
Hematologic Toxicity ◽  
Eligibility Criteria ◽  
Grade 3

Purpose: Two consecutive compassionate use studies of oxaliplatin were conducted in the United States and Canada in more than 5,000 patients with locally advanced or metastatic colorectal carcinoma who had experienced treatment failure after at least one prior chemotherapy regimen. Patients and Methods: The main focus was safety. Patients were assigned to treatment with either single-agent oxaliplatin or oxaliplatin in combination with fluorouracil (FU) and with or without leucovorin (LV) in various regimens. Response data collection was not a trial objective, but time to treatment failure (TTF) was recorded in the first cohort (1,370 patients). Results: All treatment regimens were well tolerated, with an overall incidence of grade 3 or 4 hematologic toxicity of 23.2%, grade 3 or 4 treatment-related gastrointestinal toxicity of 26.4% (including diarrhea, vomiting, and mucositis), and grade 3 neurosensory toxicity 3.9%. Similar results were reported in the second cohort (3,806 patients), in which the eligibility criteria were much less restrictive. In the first cohort (in which 83% received prior irinotecan), median TTF was 14 weeks, and was similar for the five regimens combining oxaliplatin and FU with or without LV, but significantly shorter for the single-agent oxaliplatin arm. The overall dose-intensity of oxaliplatin was maintained at 85.5% (range, 80.6% to 94.3%) of that prescribed by protocol (average 36.7 mg/m2/wk). Conclusion: These data in a heavily pretreated patient population confirm that oxaliplatin is safe when used as a single agent or with a variety of FU-based regimens as salvage therapy in patients with advanced colorectal cancer.

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