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*Read only for medical professionals Reference Bevacizumab in combination with chemotherapy resulted in up to 20 months PFS in patients with stage IV colon cancer with multiple systemic metastases
.
This case is a patient with stage IV colon cancer, secondary intestinal obstruction, and multiple metastases throughout the body
.
He was admitted to the hospital in August 2019 due to symptoms of intestinal obstruction, after emergency surgery to remove the colon tumor and relieve the obstruction
.
The patients were treated with the combination of bevacizumab + double-drug chemotherapy in the first-line treatment.
During the treatment, the liver metastases of the patients gradually shrunk until they disappeared.
The abdominal CT showed no signs of recurrence of intra-abdominal tumor metastasis, and the patients maintained a complete remission (CR) state for a long time until they disappeared.
Patients discontinued treatment on their own and had progression-free survival (PFS) of up to 20 months
.
Case review Basic situation: The patient was 67 years old and was admitted to hospital for "abdominal pain and discomfort for 3 days"
.
With a history of diabetes, he took "Metformin Sustained-Release Tablets" by himself, and his blood sugar control was acceptable
.
Denied trauma and other medical history, no smoking and drinking history, no family history of tumor
.
Preoperative diagnosis and treatment: On August 30, 2019, the patient was admitted to the hospital due to "abdominal pain and discomfort for 3 days"
.
The abdominal CT examination on admission showed that the intestinal wall of the transverse colon was irregularly thickened, the border was unclear, the surrounding fat space was blurred, and small lymph node shadows were seen
.
The upper intestinal canal was significantly dilated, and multiple gas-liquid levels were seen
.
There are multiple hypodense shadows in the liver with unclear boundaries
.
Conclusion: Transverse colon cancer with multiple intrahepatic metastasis, with secondary colon and small bowel obstruction
.
A small amount of fluid in the abdominal cavity
.
Surgery: On August 31, 2019, the patient underwent "transverse colon tumor resection + colostomy".
During the operation, the colonic mass was hard and narrowed, invading the gastric antrum, and the gastric antrum could be palpated 1cm*2cm hard.
Nodules, multiple enlarged lymph nodes at the root of the transverse mesocolon, palpable 1cm*1cm hard nodules in the sixth segment of the right lobe of the liver, and scattered hard nodules in the small mesentery
.
Postoperative pathological examination: peripheral colonic moderately differentiated adenocarcinoma, the tumor size is about 4cm*3.
5cm*1cm, the cancer tissue has penetrated the muscularis propria of the intestinal wall, and vascular tumor thrombus can be seen
.
Cancer metastases were seen in surrounding lymph nodes (8/40)
.
Immunohistochemical tips: CDX-2 (+), CK20 (+), CK7 (-), Ki-67 (+, about 50%), MLH1 (+), MSH2 (+), MSH6 (+), PMS2 ( +)
.
Postoperative diagnosis: Transverse colon moderately differentiated adenocarcinoma with multiple metastases (gastric antrum, liver, peritoneum, abdominal lymph nodes)
.
Tumor stage: pT4bN2bM1c, IVC stage
.
First-line postoperative treatment: The patient was readmitted for further treatment after surgery on September 22, 2019
.
Repeat abdominal CT showed: after colon cancer, the upper part of the anastomosis contained gas
.
There were multiple low-density shadows in the liver, and there was no significant change compared with August 30, 2019
.
Figure 1 The first postoperative abdominal CT results on September 22, 2019 After admission on September 22, 2019, the patient was given oxaliplatin 200mg ivgtt d1 + capecitabine 1.
5g po d1-14, q21d (CAPEOX) combination therapy
.
The second cycle of treatment started with bevacizumab 350mg ivgtt q3w for 8 cycles
.
Review during treatment and evaluation of efficacy: On November 3, 2019, after the patient completed 2 cycles of combined therapy, abdominal CT was re-examined.
Prompt: after colon cancer surgery, compared with (September 22, 2019) imaging, intrahepatic low-density lesions Significantly less than before, the scope narrowed
.
Efficacy assessment: partial remission (PR)
.
Figure 2 On November 3, 2019, abdominal CT reexamination after 2 cycles of treatment On December 15, 2019, after the patient completed 4 cycles of combined treatment, the reexamination of abdominal CT showed that: after colon cancer surgery, the intrahepatic metastases disappeared and no obvious intra-abdominal lesions were seen.
Tumor metastasis and recurrence
.
Efficacy assessment: complete remission (CR)
.
Figure 3 Abdominal CT reexamination after 4 cycles of treatment on December 15, 2019 On March 17, 2020, and August 26, 2020, the patient underwent abdominal CT reexamination respectively, indicating that there were no obvious signs of tumor metastasis or recurrence in the abdominal cavity
.
Good tumor control, efficacy evaluation: CR
.
After 8 cycles of combination therapy, the patient refused to continue maintenance therapy
.
In May 2021, the patient's abdominal CT showed progression of the disease
.
At this time, the patient had a PFS of up to 20 months during first-line therapy
.
Adverse reaction management: There were no obvious drug-related adverse reactions during the patient's treatment, and the patient's treatment was well tolerated
.
Case discussion ▌ Stage IV colon cancer with multiple metastases throughout the body—seeking hope in a difficult treatment Colorectal cancer (CRC) has become a malignant disease that seriously threatens the lives and health of Chinese residents, causing a serious social burden
.
In 2020, there were about 555,000 new cases of CRC in China, accounting for 12.
2% of the number of new cancers in China that year
.
There were 286,000 deaths, accounting for 9.
5% of cancer deaths in China that year [1]
.
And 83% of CRC patients are in the middle and late stages at the time of diagnosis, missing the opportunity of surgical treatment [2]
.
The liver is the most important target organ for hematogenous metastasis of colorectal cancer, and liver metastasis is also one of the key and difficult points in the treatment of colorectal cancer
.
Relevant studies have shown that about 15%-25% of colorectal cancer patients have already developed liver metastases at the time of diagnosis
.
Among them, 80%-90% of patients with liver metastases cannot obtain radical resection
.
Liver metastasis is also the main cause of death in patients with colorectal cancer [3]
.
Professor Yin Haiqing introduced that the above-mentioned team treated an elderly male patient who was admitted to the hospital for symptoms related to intestinal obstruction such as "abdominal pain and discomfort"
.
The first abdominal CT examination after admission showed: considering transverse colon cancer with multiple intrahepatic metastases, secondary colon and small bowel obstruction, and a small amount of peritoneal effusion
.
For patients with early unresectable advanced colon cancer with obvious symptoms of intestinal obstruction and multiple liver metastases
.
According to the recommendation of the "2019 Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer Diagnosis and Treatment Guidelines" [4], emergency "transverse colon tumor resection + colostomy" should be performed for patients to relieve obstruction in advance and then perform systemic treatment
.
Intraoperative findings of tumor metastasis in the patient were not optimistic
.
Professor Yin Haiqing said that the patient's transverse colon tumor had penetrated the intestinal wall and entered the fat layer
.
Tumor metastatic hard lesions were seen in the gastric antrum, and there were multiple enlarged lymph nodes at the root of the transverse mesocolon, and metastasis was considered
.
Hard nodules were palpable in segment 6 of the right lobe of the liver, and there were scattered hard nodules in the small mesentery
.
Postoperative pathological examination confirmed that the patient's transverse colon moderately differentiated adenocarcinoma had metastasized to gastric antrum, liver, peritoneum and abdominal lymph nodes
.
Tumor stage: pT4bN2bM1c, IVC stage
.
Based on the patient's multiple metastases from colon cancer, there is no potential for resection
.
According to the recommendations of the "2019 CSCO Colorectal Cancer Diagnosis and Treatment Guidelines", regardless of the RAS/BRAF mutation status, the first-line treatment of patients with tumors originating in the right colon is the first-line treatment with bevacizumab combined with chemotherapy
.
The patients were treated with CAPEOX regimen + bevacizumab combination therapy 3 weeks after operation
.
After completing 2 cycles of treatment, re-examination of abdominal CT showed that the intrahepatic low-density foci were significantly reduced and the scope narrowed
.
Efficacy assessment: PR
.
After several imaging examinations during the treatment, no liver metastases were found, and the efficacy evaluation reached CR
.
Although the patient refused to continue maintenance therapy until the lesion progressed after 8 cycles of treatment, the patient's PFS was still up to 20 months with CAPEOX+bevacizumab palliative first-line therapy
.
And no serious adverse drug-related reactions occurred during the treatment period, and the patient's treatment tolerance was good
.
▌ Bevacizumab combined with chemotherapy - "golden partner" for patients with advanced right colon cancer Regarding the application of targeted therapy drugs in the field of colorectal cancer, Professor Yin Haiqing said that with targeted and immunotherapy in the field of malignant tumor treatment Since 2004, colorectal cancer has also entered the era of targeted therapy in an all-round way
.
Compared with traditional chemotherapy, dual-drug chemotherapy combined with targeted therapy significantly improves the survival time of patients
.
Targeted therapy drugs represented by bevacizumab and cetuximab have also been recommended by authoritative guidelines for drug treatment of advanced colorectal cancer
.
The latest "2021 CSCO Colorectal Cancer Diagnosis and Treatment Guidelines" [5] recommends first-line regimens for palliative treatment of metastatic colorectal cancer: patients with primary lesions located in the right colon, regardless of RAS/BRAF mutation status, are the first to recommend bevacizumab Anti-combination chemotherapy regimens
.
This makes this program a 'golden partner' for first-line treatment of patients with primary right-sided colon cancer
.
"Professor Yin Haiqing said that bevacizumab can selectively bind to VEGF to block its biological activity, reduce tumor angiogenesis, and thus inhibit tumor growth
.
As a classic anti-angiogenesis drug, bevacizumab has become a late-stage drug.
It is an important means for the treatment of colorectal cancer
.
The results of the comparative study on the pharmaceutical, non-clinical and clinical similarity of bevacizumab biosimilars and the original research drugs show that the pharmaceutical characteristics, non-clinical characteristics of bevacizumab biosimilars and the original research drugs The clinical characteristics and human pharmacokinetic characteristics are highly similar, the clinical efficacy is equivalent, the safety is similar, and the immunogenicity is similar
.
The safety of domestic biosimilars of bevacizumab is similar to that of the original bevacizumab in terms of relevant equivalence studies and clinical efficacy observations
.
As long as the patient's medication indications are correctly evaluated and adverse reactions are promptly and correctly handled, it is possible to To maximize the benefits of mCRC patients
.
The standardized application of bevacizumab combined with chemotherapy in the real world will surely further benefit more advanced colorectal cancer patients
.
Expert Profile Yin Haiqing, Deputy Chief Physician, Deputy Chief Physician, Deputy Director, and Head of the Department of Oncology, Henan Hongli Hospital, Member of the Tumor Palliative and Rehabilitation Treatment Committee of Henan Anti-Cancer Association, Member of Henan Anti-Cancer Association Tumor Prevention and Science Popularization Committee, Xinxiang Anti-Cancer Association Chemotherapy The Standing Committee Member of the Special Committee, 2016 Outstanding Trainee Physician of Fudan University Affiliated Cancer Hospital, Henan Provincial Department of Science and Technology Science and Technology Achievement (the first person to complete one), published more than ten papers in Peking University Core, Statistical Source Core, and National Papers References: [1] IRAC 2020 Global Cancer Burden Report [2] Beijing Aipu Cancer Patient Care Foundation, School of Public Health of Peking Union Medical College "Survey on the Status of Diagnosis and Treatment of Advanced Colorectal Cancer Patients in China" [3] Chinese Medical Doctor Association Surgeons Branch, Chinese Medical Association "Guidelines for Diagnosis and Comprehensive Treatment of Colorectal Cancer Liver Metastasis in China 2020 Edition" by the Gastrointestinal Surgery Group of the Surgical Branch.
Chinese Clinical Medicine, Vol.
28, No.
1, February 2021 [4] 2019 edition of "Chinese Society of Clinical Oncology (CSCO) Colorectum" Cancer Diagnosis and Treatment Guidelines [5] 2021 edition of the Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer Diagnosis and Treatment Guidelines The interview/writing/publishing of this article is supported by AstraZeneca and is for reference only by healthcare professionals
.
Approval number CN-91341 Expiration date 2023-2-16*This article is only for providing scientific information to medical professionals and does not represent the views of this platform
.
This case is a patient with stage IV colon cancer, secondary intestinal obstruction, and multiple metastases throughout the body
.
He was admitted to the hospital in August 2019 due to symptoms of intestinal obstruction, after emergency surgery to remove the colon tumor and relieve the obstruction
.
The patients were treated with the combination of bevacizumab + double-drug chemotherapy in the first-line treatment.
During the treatment, the liver metastases of the patients gradually shrunk until they disappeared.
The abdominal CT showed no signs of recurrence of intra-abdominal tumor metastasis, and the patients maintained a complete remission (CR) state for a long time until they disappeared.
Patients discontinued treatment on their own and had progression-free survival (PFS) of up to 20 months
.
Case review Basic situation: The patient was 67 years old and was admitted to hospital for "abdominal pain and discomfort for 3 days"
.
With a history of diabetes, he took "Metformin Sustained-Release Tablets" by himself, and his blood sugar control was acceptable
.
Denied trauma and other medical history, no smoking and drinking history, no family history of tumor
.
Preoperative diagnosis and treatment: On August 30, 2019, the patient was admitted to the hospital due to "abdominal pain and discomfort for 3 days"
.
The abdominal CT examination on admission showed that the intestinal wall of the transverse colon was irregularly thickened, the border was unclear, the surrounding fat space was blurred, and small lymph node shadows were seen
.
The upper intestinal canal was significantly dilated, and multiple gas-liquid levels were seen
.
There are multiple hypodense shadows in the liver with unclear boundaries
.
Conclusion: Transverse colon cancer with multiple intrahepatic metastasis, with secondary colon and small bowel obstruction
.
A small amount of fluid in the abdominal cavity
.
Surgery: On August 31, 2019, the patient underwent "transverse colon tumor resection + colostomy".
During the operation, the colonic mass was hard and narrowed, invading the gastric antrum, and the gastric antrum could be palpated 1cm*2cm hard.
Nodules, multiple enlarged lymph nodes at the root of the transverse mesocolon, palpable 1cm*1cm hard nodules in the sixth segment of the right lobe of the liver, and scattered hard nodules in the small mesentery
.
Postoperative pathological examination: peripheral colonic moderately differentiated adenocarcinoma, the tumor size is about 4cm*3.
5cm*1cm, the cancer tissue has penetrated the muscularis propria of the intestinal wall, and vascular tumor thrombus can be seen
.
Cancer metastases were seen in surrounding lymph nodes (8/40)
.
Immunohistochemical tips: CDX-2 (+), CK20 (+), CK7 (-), Ki-67 (+, about 50%), MLH1 (+), MSH2 (+), MSH6 (+), PMS2 ( +)
.
Postoperative diagnosis: Transverse colon moderately differentiated adenocarcinoma with multiple metastases (gastric antrum, liver, peritoneum, abdominal lymph nodes)
.
Tumor stage: pT4bN2bM1c, IVC stage
.
First-line postoperative treatment: The patient was readmitted for further treatment after surgery on September 22, 2019
.
Repeat abdominal CT showed: after colon cancer, the upper part of the anastomosis contained gas
.
There were multiple low-density shadows in the liver, and there was no significant change compared with August 30, 2019
.
Figure 1 The first postoperative abdominal CT results on September 22, 2019 After admission on September 22, 2019, the patient was given oxaliplatin 200mg ivgtt d1 + capecitabine 1.
5g po d1-14, q21d (CAPEOX) combination therapy
.
The second cycle of treatment started with bevacizumab 350mg ivgtt q3w for 8 cycles
.
Review during treatment and evaluation of efficacy: On November 3, 2019, after the patient completed 2 cycles of combined therapy, abdominal CT was re-examined.
Prompt: after colon cancer surgery, compared with (September 22, 2019) imaging, intrahepatic low-density lesions Significantly less than before, the scope narrowed
.
Efficacy assessment: partial remission (PR)
.
Figure 2 On November 3, 2019, abdominal CT reexamination after 2 cycles of treatment On December 15, 2019, after the patient completed 4 cycles of combined treatment, the reexamination of abdominal CT showed that: after colon cancer surgery, the intrahepatic metastases disappeared and no obvious intra-abdominal lesions were seen.
Tumor metastasis and recurrence
.
Efficacy assessment: complete remission (CR)
.
Figure 3 Abdominal CT reexamination after 4 cycles of treatment on December 15, 2019 On March 17, 2020, and August 26, 2020, the patient underwent abdominal CT reexamination respectively, indicating that there were no obvious signs of tumor metastasis or recurrence in the abdominal cavity
.
Good tumor control, efficacy evaluation: CR
.
After 8 cycles of combination therapy, the patient refused to continue maintenance therapy
.
In May 2021, the patient's abdominal CT showed progression of the disease
.
At this time, the patient had a PFS of up to 20 months during first-line therapy
.
Adverse reaction management: There were no obvious drug-related adverse reactions during the patient's treatment, and the patient's treatment was well tolerated
.
Case discussion ▌ Stage IV colon cancer with multiple metastases throughout the body—seeking hope in a difficult treatment Colorectal cancer (CRC) has become a malignant disease that seriously threatens the lives and health of Chinese residents, causing a serious social burden
.
In 2020, there were about 555,000 new cases of CRC in China, accounting for 12.
2% of the number of new cancers in China that year
.
There were 286,000 deaths, accounting for 9.
5% of cancer deaths in China that year [1]
.
And 83% of CRC patients are in the middle and late stages at the time of diagnosis, missing the opportunity of surgical treatment [2]
.
The liver is the most important target organ for hematogenous metastasis of colorectal cancer, and liver metastasis is also one of the key and difficult points in the treatment of colorectal cancer
.
Relevant studies have shown that about 15%-25% of colorectal cancer patients have already developed liver metastases at the time of diagnosis
.
Among them, 80%-90% of patients with liver metastases cannot obtain radical resection
.
Liver metastasis is also the main cause of death in patients with colorectal cancer [3]
.
Professor Yin Haiqing introduced that the above-mentioned team treated an elderly male patient who was admitted to the hospital for symptoms related to intestinal obstruction such as "abdominal pain and discomfort"
.
The first abdominal CT examination after admission showed: considering transverse colon cancer with multiple intrahepatic metastases, secondary colon and small bowel obstruction, and a small amount of peritoneal effusion
.
For patients with early unresectable advanced colon cancer with obvious symptoms of intestinal obstruction and multiple liver metastases
.
According to the recommendation of the "2019 Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer Diagnosis and Treatment Guidelines" [4], emergency "transverse colon tumor resection + colostomy" should be performed for patients to relieve obstruction in advance and then perform systemic treatment
.
Intraoperative findings of tumor metastasis in the patient were not optimistic
.
Professor Yin Haiqing said that the patient's transverse colon tumor had penetrated the intestinal wall and entered the fat layer
.
Tumor metastatic hard lesions were seen in the gastric antrum, and there were multiple enlarged lymph nodes at the root of the transverse mesocolon, and metastasis was considered
.
Hard nodules were palpable in segment 6 of the right lobe of the liver, and there were scattered hard nodules in the small mesentery
.
Postoperative pathological examination confirmed that the patient's transverse colon moderately differentiated adenocarcinoma had metastasized to gastric antrum, liver, peritoneum and abdominal lymph nodes
.
Tumor stage: pT4bN2bM1c, IVC stage
.
Based on the patient's multiple metastases from colon cancer, there is no potential for resection
.
According to the recommendations of the "2019 CSCO Colorectal Cancer Diagnosis and Treatment Guidelines", regardless of the RAS/BRAF mutation status, the first-line treatment of patients with tumors originating in the right colon is the first-line treatment with bevacizumab combined with chemotherapy
.
The patients were treated with CAPEOX regimen + bevacizumab combination therapy 3 weeks after operation
.
After completing 2 cycles of treatment, re-examination of abdominal CT showed that the intrahepatic low-density foci were significantly reduced and the scope narrowed
.
Efficacy assessment: PR
.
After several imaging examinations during the treatment, no liver metastases were found, and the efficacy evaluation reached CR
.
Although the patient refused to continue maintenance therapy until the lesion progressed after 8 cycles of treatment, the patient's PFS was still up to 20 months with CAPEOX+bevacizumab palliative first-line therapy
.
And no serious adverse drug-related reactions occurred during the treatment period, and the patient's treatment tolerance was good
.
▌ Bevacizumab combined with chemotherapy - "golden partner" for patients with advanced right colon cancer Regarding the application of targeted therapy drugs in the field of colorectal cancer, Professor Yin Haiqing said that with targeted and immunotherapy in the field of malignant tumor treatment Since 2004, colorectal cancer has also entered the era of targeted therapy in an all-round way
.
Compared with traditional chemotherapy, dual-drug chemotherapy combined with targeted therapy significantly improves the survival time of patients
.
Targeted therapy drugs represented by bevacizumab and cetuximab have also been recommended by authoritative guidelines for drug treatment of advanced colorectal cancer
.
The latest "2021 CSCO Colorectal Cancer Diagnosis and Treatment Guidelines" [5] recommends first-line regimens for palliative treatment of metastatic colorectal cancer: patients with primary lesions located in the right colon, regardless of RAS/BRAF mutation status, are the first to recommend bevacizumab Anti-combination chemotherapy regimens
.
This makes this program a 'golden partner' for first-line treatment of patients with primary right-sided colon cancer
.
"Professor Yin Haiqing said that bevacizumab can selectively bind to VEGF to block its biological activity, reduce tumor angiogenesis, and thus inhibit tumor growth
.
As a classic anti-angiogenesis drug, bevacizumab has become a late-stage drug.
It is an important means for the treatment of colorectal cancer
.
The results of the comparative study on the pharmaceutical, non-clinical and clinical similarity of bevacizumab biosimilars and the original research drugs show that the pharmaceutical characteristics, non-clinical characteristics of bevacizumab biosimilars and the original research drugs The clinical characteristics and human pharmacokinetic characteristics are highly similar, the clinical efficacy is equivalent, the safety is similar, and the immunogenicity is similar
.
The safety of domestic biosimilars of bevacizumab is similar to that of the original bevacizumab in terms of relevant equivalence studies and clinical efficacy observations
.
As long as the patient's medication indications are correctly evaluated and adverse reactions are promptly and correctly handled, it is possible to To maximize the benefits of mCRC patients
.
The standardized application of bevacizumab combined with chemotherapy in the real world will surely further benefit more advanced colorectal cancer patients
.
Expert Profile Yin Haiqing, Deputy Chief Physician, Deputy Chief Physician, Deputy Director, and Head of the Department of Oncology, Henan Hongli Hospital, Member of the Tumor Palliative and Rehabilitation Treatment Committee of Henan Anti-Cancer Association, Member of Henan Anti-Cancer Association Tumor Prevention and Science Popularization Committee, Xinxiang Anti-Cancer Association Chemotherapy The Standing Committee Member of the Special Committee, 2016 Outstanding Trainee Physician of Fudan University Affiliated Cancer Hospital, Henan Provincial Department of Science and Technology Science and Technology Achievement (the first person to complete one), published more than ten papers in Peking University Core, Statistical Source Core, and National Papers References: [1] IRAC 2020 Global Cancer Burden Report [2] Beijing Aipu Cancer Patient Care Foundation, School of Public Health of Peking Union Medical College "Survey on the Status of Diagnosis and Treatment of Advanced Colorectal Cancer Patients in China" [3] Chinese Medical Doctor Association Surgeons Branch, Chinese Medical Association "Guidelines for Diagnosis and Comprehensive Treatment of Colorectal Cancer Liver Metastasis in China 2020 Edition" by the Gastrointestinal Surgery Group of the Surgical Branch.
Chinese Clinical Medicine, Vol.
28, No.
1, February 2021 [4] 2019 edition of "Chinese Society of Clinical Oncology (CSCO) Colorectum" Cancer Diagnosis and Treatment Guidelines [5] 2021 edition of the Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer Diagnosis and Treatment Guidelines The interview/writing/publishing of this article is supported by AstraZeneca and is for reference only by healthcare professionals
.
Approval number CN-91341 Expiration date 2023-2-16*This article is only for providing scientific information to medical professionals and does not represent the views of this platform
