Predictive markers for the treatment of colorectal cancer with cetuximab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13500-13500 ◽  
Author(s):  
E. Razis ◽  
E. Briasoulis ◽  
I. Kostopoulos ◽  
M. Bobos ◽  
C. Christodoulou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Agent ◽  
Skin Toxicity ◽  
Complete Response ◽  
Response To Therapy ◽  
Egfr Expression ◽  
Gene Status ◽  
Line Of Therapy ◽  
Colorectal Cancer Patients ◽  
Line P

13500 Background: Cetuximab is an anti-EGFR monoclonal antibody with activity in colorectal cancer. Patients most likely to benefit should be identified using molecular markers. Methods: A retrospective analysis was performed on patients treated with cetuximab who had paraffin embedded tissue available for testing. Tumor specimens were tested for EGFR (31G7, Zymed), PTEN (28H6, Novocastra) and pAkt 1/2/3 (Thr 308, Santa Cruz) expression by IHC. The EGFR gene status was investigated by FISH (Vysis). Results: Seventy-two patients were identified. EGFR expression was detected in 32/68 patients tested. PTEN was positive in all cases tested (64/64) and pAkt in 52 of 64 patients, in >70% of cells in 21/64 cases. Most patients were treated with cetuximab in various combinations, three patients received it as a single agent and 7 patients in more than one line of therapy. Median follow-up from diagnosis was 30.7 months and from Cetuximab initiation 6.9 months. Median survival from diagnosis has not been reached yet but from initiation of Cetuximab it is 13.6 months. 19 patients achieved a PR and 1 a CR. Most patients with PR were treated in first or second line however, 6 patients achieved a PR in 3rd line and 3 in subsequent lines. The patient with complete response, was treated in first line with CPT 11 and Cetuximab. TTP was 7.4 months for patients treated with Cetuximab in 1st line, 7.5 in 2nd line and 5.3 in 3rd line. Survival did not correlate significantly with any of the immunohistochemically assessed parameters. TTP correlated significantly with pAkt overexpression for patients treated in 3rd line (p=0.0065). The CR was seen in the only patient with EGFR amplification.The presence of skin toxicity did not correlate with response to therapy. Conclusions: Overexpression of pAkt may correlate with response to Cetuximab in colorectal cancer. No significant financial relationships to disclose.

Combination intraventricular chemotherapy for meningeal neoplasia.

1986 ◽  
Vol 4 (1) ◽  
pp. 68-73 ◽  
Author(s):  
L Giannone ◽  
F A Greco ◽  
J D Hainsworth
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Transitional Cell ◽  
Response Duration ◽  
Complete Response ◽  
Response To Therapy ◽  
Entire Group ◽  
Intraventricular Chemotherapy ◽  
Wbc Count

Twenty two patients with meningeal neoplasia were treated with biweekly combination intraventricular chemotherapy using methotrexate, cytosine arabinoside, and thiotepa. Patients with the following malignancies were included: breast cancer, ten patients; lung cancer, seven; non-Hodgkin's lymphoma, two; malignant melanoma, one; transitional cell carcinoma of the bladder, one; and malignant glioma, one. Eight of 22 patients (36%) had a Karnofsky performance status of less than 50%. Eleven of 22 patients received radiotherapy to symptomatic areas, and seven received systemic chemotherapy in addition to combination intraventricular therapy. Patients were evaluated for both toxicity and response to therapy. Myelosuppression was the major toxic condition and occurred in 17 of 22 patients (77%). Ten patients (45%) had a nadir WBC count of less than 1000/microL or a platelet count of less than 25,000/microL. No patient achieved a complete response (CR), although nine patients (41%) had partial responses (PRs) lasting 4 to 24 + weeks. Median survival for the entire group was 10 weeks (range, 6 to 24+ weeks). In this small group of patients, simultaneous triple-drug intraventricular chemotherapy caused unacceptable myelosuppression without increasing the response rate, response duration, or survival when compared with single-agent methotrexate and radiotherapy.

A case of unexpected peripherally inserted central catheter removal from a colorectal cancer patient with cetuximab-induced skin toxicity and contact dermatitis at the peripherally inserted central catheter insertion site: Should we recommend the patient to choose subcutaneous port preferentially?

2020 ◽  
pp. 112972982091088
Author(s):  
Hui Yang ◽  
Yuanyi Rui ◽  
Guorong Wang
Keyword(s):  
Colorectal Cancer ◽  
Contact Dermatitis ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Insertion Site ◽  
Skin Toxicity ◽  
Peripherally Inserted Central Catheter ◽  
Central Catheter ◽  
Catheter Insertion Site ◽  
Colorectal Cancer Patients

Introduction: Obtaining central venous access is one of the most commonly performed procedures in cancer patients. However, there are very limited data to guide clinicians when selecting a device for metastatic colorectal cancer patients who received cetuximab. Case description: A 54-year-old male patient with metastatic colorectal cancer treated with cetuximab plus FOLFIRI used peripherally inserted central catheter as intravenous pathway. After eight cycles, the patient suffered cetuximab-induced grade 2 skin toxicity and grade 3 contact dermatitis at the peripherally inserted central catheter insertion site. Finally, he removed the peripherally inserted central catheter and accepted subcutaneous port instead for 2 years without implantation cutaneous complication. Conclusions: We suggest that metastatic colorectal cancer patients treated with cetuximab should be recommended to choose subcutaneous port preferentially to avoid potential risk of unexpected peripherally inserted central catheter removal due to cetuximab-induced skin toxicity or contact dermatitis. Further clinical practices and researches are needed for more profound evidences for better practical suggestions.

Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1337-1345 ◽  
Author(s):  
Eric Van Cutsem ◽  
Michael Findlay ◽  
Bruno Osterwalder ◽  
Walter Kocha ◽  
David Dalley ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Dose Intensity ◽  
Patient Characteristics ◽  
Complete Response ◽  
Phase Iii ◽  
Effective Treatment Option ◽  
Randomized Phase Ii

PURPOSE: To evaluate in patients with advanced colorectal cancer (CRC) three treatment regimens of oral capecitabine in order to select the most appropriate regimen for testing in phase III. PATIENTS AND METHODS: Three capecitabine schedules were evaluated in a randomized phase II design: arm A, 1,331 mg/m2/d bid continuously; arm B, 2,510 mg/m2/d bid intermittently (2 weeks on/1 week off); and arm C, 1,657 mg/m2/d plus oral leucovorin 60 mg/d bid intermittently (2 weeks on/1 week off). RESULTS: One hundred nine patients were randomized; 39 patients were assessable for efficacy in arm A, 34 in arm B, and 35 in arm C. Patient characteristics were balanced in the arms. Confirmed tumor responses (partial response [PR] + complete response [CR]) were reported for eight patients with two CRs (21%; 95% confidence interval [CI], 9% to 36%) in arm A, eight patients with one CR (24%; 95% CI, 11% to 41%) in arm B, and eight patients with two CRs (23%; 95% CI, 10% to 40%) in arm C. Median times to progression (TTP) in arms A, B, and C were 127, 230, and 165 days, respectively. Overall, more toxicity was seen with capecitabine plus leucovorin, particularly diarrhea and hand-foot syndrome. There was no grade 3 or 4 marrow toxicity. CONCLUSION: Capecitabine offers a new, effective treatment option as an oral single agent in advanced CRC. Promising overall response rates were reported for all three regimens. The addition of leucovorin to the intermittent regimen had no marked effect on tumor response or median TTP. The intermittent single-agent capecitabine schedule is proposed for phase III evaluation, based on considerations of toxicity, dose-intensity, response rate, and TTP.

scholarly journals Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208080 ◽  
Author(s):  
Jara Baas ◽  
Lisanne Krens ◽  
Stefan Bohringer ◽  
Linda Mol ◽  
Cornelis Punt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Association Study ◽  
Cancer Patients ◽  
Genome Wide Association Study ◽  
Skin Toxicity ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Colorectal Cancer Patients

scholarly journals Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ji-Lin Li ◽  
Shu-Han Lin ◽  
Hong-Qiu Chen ◽  
Li-Sheng Liang ◽  
Xian-Wei Mo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Ovarian Metastasis ◽  
Egfr Expression ◽  
Colorectal Cancer Patients

scholarly journals Single agent panitumumab in KRAS wild-type metastatic colorectal cancer patients following cetuximab-based regimens

2013 ◽  
Vol 14 (12) ◽  
pp. 1098-1103 ◽  
Author(s):  
Filippo Pietrantonio ◽  
Federica Perrone ◽  
Pamela Biondani ◽  
Claudia Maggi ◽  
Andrea Lampis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Single Agent ◽  
Wild Type ◽  
Colorectal Cancer Patients

Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors That Do Not Express the Epidermal Growth Factor Receptor by Immunohistochemistry

2005 ◽  
Vol 23 (9) ◽  
pp. 1803-1810 ◽  
Author(s):  
Ki Young Chung ◽  
Jinru Shia ◽  
Nancy E. Kemeny ◽  
Manish Shah ◽  
Gary K. Schwartz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Pathology Report ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Colorectal Cancer Patients

Purpose To establish evidence of activity, or lack thereof, of cetuximab-based therapy in patients with refractory colorectal cancer with tumors that do not demonstrate epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC). Patients and Methods Pharmacy computer records were reviewed to identify all patients who received cetuximab at Memorial Sloan-Kettering Cancer Center in a nonstudy setting during the first 3 months of cetuximab's commercial availability. Medical records of these patients were then reviewed to identify colorectal cancer patients who had experienced failure with a prior irinotecan-based regimen and who had a pathology report indicating an EGFR-negative tumor by IHC. Pathology slides from these patients were reviewed by a reference pathologist to confirm EGFR negativity, and computed tomography scans during cetuximab-based therapy were reviewed by a reference radiologist. Response rates were reported using WHO criteria. Results Sixteen chemotherapy-refractory, EGFR-negative colorectal cancer patients who received cetuximab in a nonstudy setting were identified. Fourteen of these patients received cetuximab plus irinotecan, and two received cetuximab monotherapy. In the 16 patients, four major objective responses were seen (response rate, 25%; 95% CI, 4% to 46%). Conclusion Colorectal cancer patients with EGFR-negative tumors have the potential to respond to cetuximab-based therapies. EGFR analysis by current IHC techniques does not seem to have predictive value, and selection or exclusion of patients for cetuximab therapy on the basis of currently available EGFR IHC does not seem warranted.

EGFR expression using immunohistochemistry (IHC) testing as a tool for selecting patients (pts) for treatment with cetuximab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13000-13000 ◽  
Author(s):  
A. L. Ervin-Haynes ◽  
R. M. Schinagl ◽  
M. R. Dalesandro ◽  
J. Roecker ◽  
H. Youssoufian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Routine Practice ◽  
Study Enrollment ◽  
Egfr Expression ◽  
Number Of Patients ◽  
The Us ◽  
Colorectal Cancer Patients ◽  
The Relationship ◽  
Cetuximab Therapy

13000 Background: EGFR expression, as determined by IHC, is currently used to select patients for cetuximab therapy. Based on prior studies in colorectal cancer patients, approximately 60 to 75% of patients express EGFR. There is increasing evidence that EGFR expression is not predictive of response to cetuximab therapy, and does not properly select patients who might benefit from such therapy (Chung et al 2005, Saltz et al 2005, Scartozi et al 2004, NCCN 2005). Such selection limits access to a considerable number of patients who might otherwise benefit. Methods: A clinical trial of cetuximab (Erbitux®) monotherapy is being conducted in 60 EGFR-undetectable patients with metastatic colorectal cancer at 14 sites in the US and Canada to explore the relationship between EGFR expression and cetuximab activity. Results: As of January 5, 2006, 112 patients have been screened. Of these patients, 33 (29%) were EGFR-undetectable and continued screening for study enrollment; 52 (46%) tested positive for EGFR expression; and 2 (2%) did not have enough tissue to evaluate EGFR status and were not enrolled onto the trial. The remaining 25 pts (22%), were initially found to be EGFR-undetectable by IHC testing at local labs, but were subsequently identified as EGFR-positive after reevaluation at a highly experienced, centralized laboratory. Conclusion: The majority of patients tested for EGFR expression are tested using the EGFR pharmDx™ IHC assay. Results of the IHC-based assay for EGFR expression are highly dependent upon sample preparation and the methods used in conducting the assay. Variability in methods among labs may result in poor identification of pts expressing EGFR. This finding, together with the growing evidence that EGFR expression is not predictive of response to cetuximab therapy, indicate that the current routine practice of tumor IHC EGFR testing for the purpose of selecting cetuximab therapy may be inappropriate and pts who could potentially benefit from cetuximab therapy are being excluded from a treatment option. [Table: see text]

First-line single-agent cetuximab in patients with advanced colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3553-3553 ◽  
Author(s):  
A. Pessino ◽  
S. Artale ◽  
A. Guglielmi ◽  
S. Sciallero ◽  
G. Fornarini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Great Majority ◽  
Skin Toxicity ◽  
Common Adverse Event ◽  
Time To Progression ◽  
Grade 3

3553 Background: The most relevant recent advance in the treatment of metastatic colorectal cancer is the fact that cure is still possible under very selected conditions. However the goal of chemotherapy remains palliative in the great majority of patients, justifying less toxic innovative approaches in so- called “window of opportunity trials”. We have pursued this idea in a phase II study of cetuximab monotherapy in chemo-naive patients with advanced colorectal cancer beyond any possibility of curative resection. Methods: Patients with non-resectable metastatic colorectal cancer (at least two metastatic sites and/or otherwise inoperable metastatic disease) were treated with cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) until progressive disease (PD) or unacceptable toxicity. The primary end-point was objective response; secondary end-points were: stable disease, time to treatment failure and time to progression. According to Simon’s two-stage design, the number of responses/patients to stop the trial was 0/10 for stage 1 and 3/29 for stage 2. Results: Of the 44 patients screened, 42 (97%) had EGFR-expressing tumors. Thirty-nine patients (median age: 69) initiated the treatment. Two had grade 3 allergic reactions to cetuximab at the first administration leading to treatment discontinuation. The most common adverse event was skin toxicity, which occurred in 90% of the patients ( 31% grade 2, 10 % grade 3). We observed 1 complete response, 3 partial responses, 13 stable diseases (5 of which were minor responses), and 22 PD. The duration of the 4 responses were 12, 9, 9 and 6 months. Median time to progression was 2.0 months. Conclusions: The study is negative because the response rate is low. However, the duration of benefit in the few responding patients is such that it is imperative to find the molecular determinants of cetuximab activity in these cases. [Table: see text]

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