Monoclonal antibodies against epidermal growth factor receptor(EGFR) are used in the treatment of advanced colorectal cancer. However, these agents can induce severe dermatological side effects that discourage their a...Monoclonal antibodies against epidermal growth factor receptor(EGFR) are used in the treatment of advanced colorectal cancer. However, these agents can induce severe dermatological side effects that discourage their administration in patients with chronic dermatological disease. EGFR plays a key role in normal skin development and immunological function, and is expressed in various tissues and organs, although contrarily, it is overexpressed in psoriasis-related skin lesions. Thus, discussion is ongoing regarding the putative pathological role and therapeutic potential of this protein. We herein report on a patient with advanced colon cancer and concomitant long-standing psoriasis vulgaris who received antiEGFR antibody monotherapy as a third-line treatment for metastatic disease. One week after the initiation of treatment, the patient's skin lesions dramatically subsided and the improvement was sustained during therapy. Based on this case, we propose that anti-EGFR antibody therapy is not necessarily contraindicated in patients with psoriasis vulgaris. Moreover, the findings reaffirmed that EGFR is an important molecule in the pathology of psoriasis.展开更多
Introduction: Panitumumab is an EGFR inhibitor approved for use in metastatic refractory colorectal cancer. It is unclear whether patients who have progressed on cetuximab may benefit from subsequent panitumumab thera...Introduction: Panitumumab is an EGFR inhibitor approved for use in metastatic refractory colorectal cancer. It is unclear whether patients who have progressed on cetuximab may benefit from subsequent panitumumab therapy. This retrospective analysis was conducted to describe the experience at The Ohio State University with panitumumab including in patients who have progressed on cetuximab. Methods: Patients who received at least 1 dose of panitumumab between September 2006 and December 2011 were identified using the hospital’s pharmacy database. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 was used to assess responses and Kaplan-Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients (median age 61 years) were identified. Sixty-seven percent of patients had tumors with wild-type KRAS, 3.4% had tumors with mutated KRAS and the KRAS status was unknown in 29.9%. Twenty-four percent of the patients had an ECOG performance status of 2 or above and 59.8% of patients had received ≥ 2 prior lines of chemotherapy. Thirty-two percent of patients received single-agent panitumumab while 68% received it in combination with chemotherapy. Of the patients with KRAS wild-type tumors, 10 (17.2%) had objective responses (3 complete, 7 partial) and 26 (44.8%) had stable disease. Median PFS and OS were 5.0 and 9.0 months. The presence of a rash, improved ECOG performance status and coadministration with either irinotecan or FOLFIRI, led to a significantly better OS in univariate analysis. Among patients who had clinical benefit with cetuximab, 71% had subsequent clinical benefit with panitumumab therapy. Conclusions: In our single institution analysis of patients who received panitumumab, the number of prior lines of therapy did not significantly affect OS, suggesting that panitumumab retains its efficacy in the 2nd and 3rd line setting. Additionally, panitumumab can benefit patients who previously had clinical benefit with cetuximab.展开更多
BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy. Prophylactic actions are recommended, but routine clinical manage...BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy. Prophylactic actions are recommended, but routine clinical management of these toxicities and their impact on quality of life remain unknown. AIM To assess the dermatological toxicities reported after panitumumab initiation, their impact on the quality of life and the clinical practices for their management. METHODS Patients included in this prospective multicenter observational study were over 18 years of age and began treatment with panitumumab for wild-type KRAS metastatic colorectal cancer. The incidence of dermatological toxicities, clinical practices for their management and impact on quality of life were recorded during a 6-mo follow-up. RESULTS Overall, 229 patients (males, 57.6%;mean age, 66.2 years) were included. At day 15, 59.3% of patients had dermatological toxicity;the rate peaked at month 2 (74.7%) and decreased at month 6 (46.5%). The most frequent dermatological toxicities were rash/acneiform rash, xerosis and skin cracks. At least one preventive treatment was administered to 65.9% of patients (oral antibiotics, 84.1%;emollients, 75.5%;both, 62.9%). The rates of patients who received at least one curative treatment peaked at month 2 (63.4%) and decreased at month 6 (44.8%). The impact of the dermatological toxicities on quality of life was limited as assessed with Dermatology Life Quality Index scores and inconvenience visual analogic scale score. The rates of topical corticosteroids administration and visits to specialists were low. CONCLUSION The rates of the different skin toxicities peaked at various times and were improved at the end of follow-up. Nevertheless, their clinical management could be optimized with a better adherence to current recommendations. The impact of skin toxicities on patient’s quality of life appeared to be limited.展开更多
Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(P...Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(PFS) and overall survival(OS) of patients with metastatic colorectal cancer(mCRC) treated with panitumumab every 3 weeks as a second line treatment.Methods: This study is a retrospective analysis of 18 patients, aged more than 18 years, with wild-type KRAS exon 2 mCRC treated with panitumumab as a second-line single agent after progression on first-line chemotherapy.Results: The median number of courses received was 10(range, 4-29), and the median duration of treatment was 30 weeks(range,12-96 weeks). After a median follow-up period of 13 months, the median PFS was 6 months(range, 4.3-7.7 months) and the median OS was 11 months(range, 7.4-14.5 months). The median PFS was 4 months for patients with < grade 2 skin toxicity and 6months(range, 4.5-7.5 months) for patients with ≥ grade 2 skin rash(P=0.05). The median OS was 9 months(range, 6.4-11.5months) and 14 months(range, 11.6-16.3 months) for the two groups of patients(P=0.002).Conclusions: Panitumumab given every 3 weeks is effective and well tolerated in patients with advanced CRC that progressed after standard chemotherapy.展开更多
BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,ow...BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic involvement.Moreover,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently unavailable.CASE SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe jaundice.Computed tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated adenocarcinoma.No RAS or BRAF mutations were detected.The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was 2.Biliary drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly initiated.Subsequently,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse events.CONCLUSION Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.展开更多
1 文献来源
Hecht JR，Mitchell E，Chidiac T，et al．A randomized phase Ⅲ B trial of chemotherapy, Bevacizumab, and Panitumumab compared with chemotherapy and Bevacizumab alone for metastatic colorectal cancer [J]. J ...1 文献来源
Hecht JR，Mitchell E，Chidiac T，et al．A randomized phase Ⅲ B trial of chemotherapy, Bevacizumab, and Panitumumab compared with chemotherapy and Bevacizumab alone for metastatic colorectal cancer [J]. J Clin Oncol, 2009, 27（5）： 672-680.展开更多
Colorectal cancer(CRC) is a significant cause of cancer-related morbidity and mortality all over the world.Improvements of cytotoxic and biologic agents have prolonged the survival in metastatic CRC(mC RC),with a medi...Colorectal cancer(CRC) is a significant cause of cancer-related morbidity and mortality all over the world.Improvements of cytotoxic and biologic agents have prolonged the survival in metastatic CRC(mC RC),with a median overall survival of approximately 2 years and more in the past two decades.The biologic agents that have proven clinical benefits in m CRC mainly target vascular endothelial growth factor(VEGF) and epidermal growth factor receptor(EGFR).In particular,bevacizumab targeting VEGF and cetuximab and panitumumab targeting EGFR have demonstrated sig-nificant survival benefits in combination with cytotoxic chemotherapy in the first-line,second-line,or salvage setting.Aflibercept,ramucirumab,and regorafenib are also used in second-line or salvage therapy.Recent retrospective analyses have shown that KRAS or NRAS mutations were negative predictive markers for anti-EGFR therapy.Based on the evidence from large rand-omized clinical trials,personalized therapy is necessary for patients with m CRC according to their tumor biology and characteristics.The aim of this paper was to summarize the results of the major randomized clinical trials and highlight the benefits of the molecular targeted agents in patients with mC RC.展开更多
Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEG...Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS(KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.展开更多
Colorectal cancer(CRC)has high incidence and mortality worldwide.In 2012,CRC was the second most prevalent cancer among males(9%)and the third among females(8%).In recent decades,standard chemotherapies protocols comb...Colorectal cancer(CRC)has high incidence and mortality worldwide.In 2012,CRC was the second most prevalent cancer among males(9%)and the third among females(8%).In recent decades,standard chemotherapies protocols combining 5-fluorouracil,leucovorin,irinotecan and oxaliplatin were important for improve survival in this set of patients.Further,biological drugs throughout epidermal growth factor receptor(EGFR)pathways showed interesting results in metastatic disease(mCRC)control when in association to standard chemotherapy regimens.Cetuximab and panitumumab are two cornerstones for mCRC treatment and are both approved in Europe and United States based on previous results phaseⅢtrials.This paper will briefly summarize those anti-EGFR therapies framework in mCRC and discusses some issues in this regard.展开更多
文摘Monoclonal antibodies against epidermal growth factor receptor(EGFR) are used in the treatment of advanced colorectal cancer. However, these agents can induce severe dermatological side effects that discourage their administration in patients with chronic dermatological disease. EGFR plays a key role in normal skin development and immunological function, and is expressed in various tissues and organs, although contrarily, it is overexpressed in psoriasis-related skin lesions. Thus, discussion is ongoing regarding the putative pathological role and therapeutic potential of this protein. We herein report on a patient with advanced colon cancer and concomitant long-standing psoriasis vulgaris who received antiEGFR antibody monotherapy as a third-line treatment for metastatic disease. One week after the initiation of treatment, the patient's skin lesions dramatically subsided and the improvement was sustained during therapy. Based on this case, we propose that anti-EGFR antibody therapy is not necessarily contraindicated in patients with psoriasis vulgaris. Moreover, the findings reaffirmed that EGFR is an important molecule in the pathology of psoriasis.
文摘Introduction: Panitumumab is an EGFR inhibitor approved for use in metastatic refractory colorectal cancer. It is unclear whether patients who have progressed on cetuximab may benefit from subsequent panitumumab therapy. This retrospective analysis was conducted to describe the experience at The Ohio State University with panitumumab including in patients who have progressed on cetuximab. Methods: Patients who received at least 1 dose of panitumumab between September 2006 and December 2011 were identified using the hospital’s pharmacy database. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 was used to assess responses and Kaplan-Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients (median age 61 years) were identified. Sixty-seven percent of patients had tumors with wild-type KRAS, 3.4% had tumors with mutated KRAS and the KRAS status was unknown in 29.9%. Twenty-four percent of the patients had an ECOG performance status of 2 or above and 59.8% of patients had received ≥ 2 prior lines of chemotherapy. Thirty-two percent of patients received single-agent panitumumab while 68% received it in combination with chemotherapy. Of the patients with KRAS wild-type tumors, 10 (17.2%) had objective responses (3 complete, 7 partial) and 26 (44.8%) had stable disease. Median PFS and OS were 5.0 and 9.0 months. The presence of a rash, improved ECOG performance status and coadministration with either irinotecan or FOLFIRI, led to a significantly better OS in univariate analysis. Among patients who had clinical benefit with cetuximab, 71% had subsequent clinical benefit with panitumumab therapy. Conclusions: In our single institution analysis of patients who received panitumumab, the number of prior lines of therapy did not significantly affect OS, suggesting that panitumumab retains its efficacy in the 2nd and 3rd line setting. Additionally, panitumumab can benefit patients who previously had clinical benefit with cetuximab.
文摘BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy. Prophylactic actions are recommended, but routine clinical management of these toxicities and their impact on quality of life remain unknown. AIM To assess the dermatological toxicities reported after panitumumab initiation, their impact on the quality of life and the clinical practices for their management. METHODS Patients included in this prospective multicenter observational study were over 18 years of age and began treatment with panitumumab for wild-type KRAS metastatic colorectal cancer. The incidence of dermatological toxicities, clinical practices for their management and impact on quality of life were recorded during a 6-mo follow-up. RESULTS Overall, 229 patients (males, 57.6%;mean age, 66.2 years) were included. At day 15, 59.3% of patients had dermatological toxicity;the rate peaked at month 2 (74.7%) and decreased at month 6 (46.5%). The most frequent dermatological toxicities were rash/acneiform rash, xerosis and skin cracks. At least one preventive treatment was administered to 65.9% of patients (oral antibiotics, 84.1%;emollients, 75.5%;both, 62.9%). The rates of patients who received at least one curative treatment peaked at month 2 (63.4%) and decreased at month 6 (44.8%). The impact of the dermatological toxicities on quality of life was limited as assessed with Dermatology Life Quality Index scores and inconvenience visual analogic scale score. The rates of topical corticosteroids administration and visits to specialists were low. CONCLUSION The rates of the different skin toxicities peaked at various times and were improved at the end of follow-up. Nevertheless, their clinical management could be optimized with a better adherence to current recommendations. The impact of skin toxicities on patient’s quality of life appeared to be limited.
文摘Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(PFS) and overall survival(OS) of patients with metastatic colorectal cancer(mCRC) treated with panitumumab every 3 weeks as a second line treatment.Methods: This study is a retrospective analysis of 18 patients, aged more than 18 years, with wild-type KRAS exon 2 mCRC treated with panitumumab as a second-line single agent after progression on first-line chemotherapy.Results: The median number of courses received was 10(range, 4-29), and the median duration of treatment was 30 weeks(range,12-96 weeks). After a median follow-up period of 13 months, the median PFS was 6 months(range, 4.3-7.7 months) and the median OS was 11 months(range, 7.4-14.5 months). The median PFS was 4 months for patients with < grade 2 skin toxicity and 6months(range, 4.5-7.5 months) for patients with ≥ grade 2 skin rash(P=0.05). The median OS was 9 months(range, 6.4-11.5months) and 14 months(range, 11.6-16.3 months) for the two groups of patients(P=0.002).Conclusions: Panitumumab given every 3 weeks is effective and well tolerated in patients with advanced CRC that progressed after standard chemotherapy.
文摘BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic involvement.Moreover,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently unavailable.CASE SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe jaundice.Computed tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated adenocarcinoma.No RAS or BRAF mutations were detected.The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was 2.Biliary drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly initiated.Subsequently,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse events.CONCLUSION Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.
文摘1 文献来源
Hecht JR，Mitchell E，Chidiac T，et al．A randomized phase Ⅲ B trial of chemotherapy, Bevacizumab, and Panitumumab compared with chemotherapy and Bevacizumab alone for metastatic colorectal cancer [J]. J Clin Oncol, 2009, 27（5）： 672-680.
文摘Colorectal cancer(CRC) is a significant cause of cancer-related morbidity and mortality all over the world.Improvements of cytotoxic and biologic agents have prolonged the survival in metastatic CRC(mC RC),with a median overall survival of approximately 2 years and more in the past two decades.The biologic agents that have proven clinical benefits in m CRC mainly target vascular endothelial growth factor(VEGF) and epidermal growth factor receptor(EGFR).In particular,bevacizumab targeting VEGF and cetuximab and panitumumab targeting EGFR have demonstrated sig-nificant survival benefits in combination with cytotoxic chemotherapy in the first-line,second-line,or salvage setting.Aflibercept,ramucirumab,and regorafenib are also used in second-line or salvage therapy.Recent retrospective analyses have shown that KRAS or NRAS mutations were negative predictive markers for anti-EGFR therapy.Based on the evidence from large rand-omized clinical trials,personalized therapy is necessary for patients with m CRC according to their tumor biology and characteristics.The aim of this paper was to summarize the results of the major randomized clinical trials and highlight the benefits of the molecular targeted agents in patients with mC RC.
文摘Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS(KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.
文摘Colorectal cancer(CRC)has high incidence and mortality worldwide.In 2012,CRC was the second most prevalent cancer among males(9%)and the third among females(8%).In recent decades,standard chemotherapies protocols combining 5-fluorouracil,leucovorin,irinotecan and oxaliplatin were important for improve survival in this set of patients.Further,biological drugs throughout epidermal growth factor receptor(EGFR)pathways showed interesting results in metastatic disease(mCRC)control when in association to standard chemotherapy regimens.Cetuximab and panitumumab are two cornerstones for mCRC treatment and are both approved in Europe and United States based on previous results phaseⅢtrials.This paper will briefly summarize those anti-EGFR therapies framework in mCRC and discusses some issues in this regard.
