Conversion Therapy Using mFOLFOX6 With Panitumumab for Unresectable Liver Metastases From Multiple Colorectal Cancers With Familial Adenomatous Polyposis

A 39-year-old man received a diagnosis of unresectable multiple liver metastases from multiple colorectal cancers with familial adenomatous polyposis. After construction of an ileostomy, modified FOLFOX6 (mFOLFOX6) with panitumumab was administrated because rectal cancer and sigmoid colon cancer are KRAS wild type. The 13 courses of chemotherapy resulted in a marked reduction in the size of liver metastases and sigmoid colon cancer. Consequently, curative resection with total colectomy, ileal pouch anal anastomosis, and liver metastasis resection with radiofrequency ablation was performed. Progression of KRAS wild-type rectal cancer after chemotherapy suggested that each clone from rectal and sigmoid colon cancer might have a different sensitivity to epidermal growth factor receptor antibody. Immunohistochemical analysis revealed loss of PTEN expression in rectal cancer compared with liver metastases from sigmoid colon cancer, showing that the difference of mFOLFOX6 with panitumumab might be related to activation of the PI3K-AKT pathway.Key words: Panitumumab, mFOLFOX6, Colorectal cancer, Liver metastases, Familial adenomatous polyposisThe only available treatment associated with long-term survival in patients with liver metastases from colorectal cancer is complete liver tumor resection, with 5-year survival rates ranging from 25% to 57%.¹ However, only 40% to 50% of patients with colorectal metastasis to the liver are eligible for surgical resection.² Therefore, other liver metastasis patients undergo palliative chemotherapy to stabilize the disease and prolong their overall survival.During the past decade, the biggest advance made regarding unresectable liver metastases from colorectal cancer has been the ability of oncologists to convert inoperable liver disease to resectable disease using various molecular targeting drugs.^3,4 Several clinical studies have shown that the association of chemotherapy with bevacizumab (vascular endothelial growth factor monoclonal antibody), or cetuximab [epidermal growth factor receptor (EGFR) monoclonal antibody] is particularly promising in improving the resectability rate and, ultimately, survival.⁵Panitumumab is a fully human monoclonal antibody that binds specifically to the EGFR, and consequently, severe panitumumab-related infusion reactions are rare. Panitumumab, when added to FOLFOX4 (folinic acid, 5-fluorouracil, and oxaliplatin), increased response rate and improved progression-free survival in previously untreated metastatic colorectal cancer.⁶ Retrospective analyses of phase 3 trials of anti-EGFR antibodies, including cetuximab and panitumumab, found KRAS status to be an important predictive marker of efficacy, with only wild-type patients benefiting from treatment.⁷Here, we report a successful conversion therapy using modified FOLFOX6 (mFOLFOX6) plus panitumumab in a patient with familial adenomatous polyposis (FAP) who had unresectable multiple liver metastases from multiple colorectal cancers. To the best of our knowledge, we are the first researchers to demonstrate treatment of multiple target tumors derived from different clones with mFOLFOX6 and panitumumab, and to show differential panitumumab sensitivity for multiple primary tumors and liver metastases.     

Liver Transplantation for Progressive Unresectable Colorectal Liver Metastases: Case Report and Review of the Literature

BackgroundPrevious dismal clinical studies have stated that colorectal cancer with unresectable liver metastases is an absolute contraindication for liver transplantation (LT). During recent decades, it has been shown that patients with colorectal cancer with liver metastasis benefited from LT, but 100% recurrence was inevitable in progressive colorectal cancer with liver metastasis.Case presentationA 61-year-old man was found at the first visit to be suffering from unresectable liver metastases of colorectal cancer. This patient underwent colorectal radical surgery and palliative treatment after the operation. During a 2-year follow-up, we found that CEA and CA199 rebounded sharply to high levels, and liver metastasis lesions increased significantly, so we made the decision to perform LT 2 years after the first surgery. Chemotherapy and sirolimus were given post-LT. Slow-growing pulmonary metastases after transplantation were found 4 months post-LT. This patient survived the next 4 months tumor-free and by now has survived 34 months free of liver tumors. Here, we review the literature on LT for progressive liver metastasis of colorectal cancer and summarize our experience from this successful case.ConclusionThis case provides vital evidence that LT is an option and can provide curative therapy for patients with advanced unresectable liver metastasis. Careful selection of patients, postoperative comprehensive treatments, and rational application of immunosuppressive agents are vital factors for favorable prognosis.     

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as second-line treatment for advanced colorectal cancer: A Japanese experience

Purpose

This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for Japanese patients with unresectable advanced or metastatic colorectal cancer.

Methods

A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment.

Results

Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval [CI], 10.5%?C35.0%). The median PFS was 5.6 months (95% CI, 4.1?C7.0 months) and the median OS was 19.6 months (95% CI, 11.4?C24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable.

Conclusion

The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population.     

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as first-line treatment for advanced colorectal cancer: A Japanese experience

Purpose

This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin in combination with levofolinate and infusion 5-fluorouracil (FOLFOX4) as first-line therapy for Japanese patients with unresectable metastatic colorectal cancer.

Methods

Sixty consecutive patients with histologically confirmed advanced or metastatic colorectal cancer were enrolled in the study. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred.

Results

Two patients were ineligible. Toxicity was evaluated in 60 patients, who had received a part or all of the protocol therapy. A partial response was observed in 20 patients. The overall response rate was 34.5% (95% CI, 22.5%?C48.1%) and the tumor control rate (partial response + stable disease) was 82.8%. The median progression-free survival was 6.9 months (95% CI, 5.1?C9.8 months), and the median overall survival was 31.5 months (95% CI, 18.1?C40.1 months). There were no toxicity-related deaths. Grade 3 or 4 neutropenia occurred in 48.3% of patients and often caused a delay in the subsequent treatment course. Mild to moderate cumulative peripheral sensory neuropathy affected 71.7% of patients.

Conclusion

The results showed good tolerability and efficacy for first-line FOLFOX4 in the treatment of patients with advanced colorectal cancer, indicating the promise of this regimen as first-line therapy for advanced colorectal cancer in the Japanese population.     

Total mesorectal excision of initially unresectable locally advanced rectal cancer infiltrating the pelvic wall after treatment with FOLFOX4 plus bevacizumab and preoperative chemoradiation: report of a case

A 60-year-old man underwent sigmoid loop colostomy for obstructive rectal cancer. Computed tomography (CT) showed a circumferential thickening of the lower rectal wall caused by a tumor invading the posterior and side pelvic wall. As we considered R0 resection too difficult, we gave the patient bevacizumab plus FOLFOX4 (oxaliplatin, leucovorin, and 5-fluorouracil). After eight courses, CT showed improvement in the rectal wall thickening but linear thickening of the mesorectal fascia remained. We therefore gave the patient chemoradiotherapy (CRT), and then 10 weeks later performed Hartmann's operation laparoscopically. Microscopic examination revealed that the tumor had been almost replaced by fibrous tissue, with only a few cancer cells left in the subserosa. The circumferential resection margin was free of cancer cells. The patient is doing well after 27 months of follow-up. This case suggests that systemic chemotherapy with FOLFOX4 plus bevacizumab prior to conventional preoperative CRT is a promising strategy for patients with initially unresectable locally advanced rectal cancer.     

腹腔镜联合辅助化疗及内镜治疗进展期结直肠癌合并腺瘤的应用研究

目的：探讨腹腔镜结直肠癌切除术加辅助化疗加二期内镜下治疗结直肠癌合并根治术切除范围外结直肠腺瘤的临床应用价值。方法：2005年1月-2010年6月对54例进展期结直肠癌合并根治术切除范围外结直肠腺瘤（〉1．0cm）的患者（研究组）行腹腔镜结直肠癌切除术加辅助化疗（FOLFOX4方案）加二期内镜下腺瘤切除的综合治疗,对同期396例单发进展期结直肠癌患者（对照组）行腹腔镜结直肠癌切除术加辅助化疗（FOLFOX4方案）。通过并发症发生率、长期随访等评价治疗效果。结果：2组患者在年龄、性别、手术方式、手术时间、术中出血量、并发症发生率、平均住院时间、肿瘤大小、淋巴结转移、TNM分期及1、3和5年存活率差异无统计学意义（P〉O．05）。研究组辅助化疗后对合并腺瘤进行内镜下切除治疗,4例出血经保守治疗后成功止血,未发生穿孔、狭窄等严重并发症;3例患者术后病理组织学检查为腺瘤癌变,其中2例癌变局限于腺瘤中,1例癌细胞侵犯达黏膜下层,该例患者再次行腹腔镜下切除,术后随访无复发。结论：腹腔镜联合辅助化疗及内镜为合并结直肠癌根治术切除范围外腺瘤的患者提供了一种安全有效的微创治疗方法,值得临床推厂和应用。     

Which Gene is a Dominant Predictor of Response During FOLFOX Chemotherapy for the Treatment of Metastatic Colorectal Cancer, the MTHFR or XRCC1 Gene?

Background Combination chemotherapy using oxaliplatin, 5-fluorouracil and folinic acid (FOLFOX) is known to be effective in the treatment of metastatic colon cancer. Genes regulating the actions of 5-fluorouracil and oxaliplatin have been identified, but precisely which gene is dominant has not yet been determined. The aim of the investigation reported here was to identify which gene polymorphism is a dominant factor in FOLFOX chemotherapy–the methylenetetrahydrofolate reductase (MTHFR) gene for 5-fluorouracil or the X-ray cross-complementing1 (XRCC1) gene for oxaliplatin.Methods Paraffin-embedded tissues from 54 patients with unresectable metastases from colorectal cancer who had undergone chemotherapy with the FOLFOX regimen were analyzed for MTHFR polymorphisms in the MTHFR gene (677C➔T, Ala➔Val mutation) and XRCC1 gene (Arg➔Gln substitution in exon 10). Response rates and survivals were compared by types of polymorphism.Results Analyses of the patterns of MTHFR polymorphism revealed that 29.6% of the patients showed no mutation, 51.6% showed heterozygous mutations, and 11.8% showed homozygous mutations. Analyses of the XRCC1 polymorphism revealed that 60.8% of the patients showed no mutation, 31.4% showed heterozygous mutations, and 7.8% showed homozygous mutations. After four cycles of chemotherapy, 3.7% showed a complete response, 57.4% showed a partial response (PD) or stable disease, and 38.9% showed PD. The MTHFR polymorphism was not significant in predicting response and 30-month-survival (P > .1), whereas the XRCC1 polymorphism was a significant prognostic factor for both response (P = .038) and survival (P = .011).Conclusions We found a higher rate of mutations in the MTHFR gene than in the XRCC1 gene in Korean colorectal cancer patients. Response to FOLFOX was better in the patient group with mutations for MTHFR and worse in the patient group with mutations for XRCC1. However, only the XRCC1 polymorphism was a significant prognostic factor for the response to FOLFOX chemotherapy and short-term survival.     

自膨式金属支架植入术治疗急性左半结直肠癌性梗阻

目的探讨内镜联合透视下自膨式金属支架植入术治疗急性左半结直肠癌性梗阻的应用价值。方法回顾性分析接受内镜联合透视下自膨式金属支架植入术治疗的49例左半结直肠癌性梗阻患者的临床资料。结果于48例患者成功植入支架,技术成功率为97.96%(48/49);1例因导丝无法通过狭窄段而转为外科急诊手术。植入支架后,47例梗阻症状明显改善;1例未改善而转为外科急诊手术。术后1例发生肠穿孔,5例便中带少量鲜血,经对症治疗后均好转;2例发生支架脱落。21例患于植入支架解除肠梗阻后接受结肠癌根治术,Ⅰ期手术成功率100%(21/21)。结论内镜联合透视下自膨式金属支架植入术解除左半结直肠癌性梗阻安全、有效。     

重组人血管内皮抑素“窗口期”联合化疗治疗晚期结直肠癌的临床研究

目的探讨重组人血管内皮抑素（恩度）“窗口期”联合化疗治疗晚期结直肠癌的有效性和安全性。方法30例晚期结直肠癌患者,采用恩度联合FOLFOX4方案化疗,恩度15mg／d,加入生理盐水500mL静滴3～4h,第1～7天,间歇7d重复给药。于应用恩度第4天开始化疗,每两周为1个周期,4个周期后评价疗效。结果28例患者可评价疗效,平均完成4．3个周期,CR0例,PR12例,SD7例,PD9例。有效率42．9％,疾病控制率67．9％,QOL改善稳定率82．1％。毒副反应主要为食欲不振、乏力。结论恩度窗口期联合化疗治疗晚期结直肠癌安全有效。     

热休克蛋白70和90表达水平与结直肠癌肝转移化疗疗效的关系

目的探讨热休克蛋白（HSP）70和HSP90的表达与结直肠癌肝转移化疗疗效的关系。方法分析52例手术切除了原发病灶而未能切除肝转移病灶并进行奥沙利铂、氟尿嘧啶及四氢叶酸钙化疗方案（FOLFOX4方案）化疗的结直肠癌肝转移患者的临床资料,通过cT检查比较化疗前后肝转移病灶数目及大小的变化：采用亲和免疫组织化学方法测定原发肿瘤组织HSP70和HSP90的表达：分析HSP70和HSP90的表达与化疗疗效间的关系。结果HSP70高表达者,部分缓解（PR）率为33．3％,低表达者PR率为64．5％,两者差异有统计学意义（P〈0．05）;HSP90高表达者,PR率为50％。低表达者PR率为53．1％,两者差异无统计学意义（P〉0．05）。结论对于HSP70低表达的结直肠癌肝转移患者．FOLFOX4方案化疗的疗效可能优于HSP70高表达者;HSP90的表达与其疗效无关。     

Surgery After Downstaging of Unresectable Hepatic Tumors With Intra-Arterial Chemotherapy

Background: This retrospective study was performed to assess the outcome among patients who underwent hepatic resection or tumor ablation after hepatic artery infusion (HAI) therapy downstaged previously unresectable hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (CRC).Methods: Between 1983 and 1998, 25 patients with HCC and 383 patients with hepatic CRC metastases were treated with HAI therapy for unresectable liver disease. We retrospectively reviewed the records of 26 (6%) of these patients who underwent subsequent surgical exploration for tumor resection or ablation.Results: At a median of 9 months (range 7–12 months) after HAI treatment, four patients (16%) with HCC underwent exploratory surgery; two underwent resection with negative margins, and the other two were given radiofrequency ablation (RFA) because of underlying cirrhosis. At a median postoperative follow-up of 16 months (range 6–48 months), all four patients were alive with no evidence of disease. At a median of 14.5 months (range 8–24 months) after HAI therapy, 22 patients with hepatic CRC metastases underwent exploratory surgery; 10 underwent resection, 6 underwent resection and RFA or cryotherapy, and 2 underwent RFA only. At a median follow-up of 17 months, 15 (83%) of the 18 patients with CRC who had received surgical treatment had developed recurrent disease; the other 3 died of other causes (1 of postoperative complications) within 7 months of the surgery. One patient in whom disease recurred underwent a second resection and was disease-free at 1 year follow-up.Conclusions: Hepatic resection or ablation after tumor downstaging with HAI therapy is a viable option for patients with unresectable HCC. However, given the high rate of recurrence of metastases from CRC, hepatic resection or ablation after downstaging with HAI should be used with caution.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16–19, 2000.     

Synchronous hepatic metastasis and metachronous Krukenberg tumor from advanced colon cancer. A case report with an unexpected disease-free survival

BackgroundIn the international literature we have never found a long survival in patients treated for a colon cancer with synchronous hepatic metastases and for a metachronous Krukenberg tumor.Presentation of caseA 46-year old woman for an advanced colon cancer with a synchronous hepatic metastases was subjected to a left hemicolectomy and a resection of liver segment V (R0 resection; T4N2bM1; stage IVa according AJCC 2010). After one year a CT of the abdomen revealed an expansive formation of the left ovary. The patient was subjected to a bilateral ovariectomy, hysterectomy and hiperthermic intraperitoneal chemotherapy (HIPEC). The patient, after several cycles of adjuvant chemotherapy, is disease-free 13 years after surgery.DiscussionTo our knowledge, in the literature there do not appear to be cases of such disease-free survival. The survival of patient despite the prognostic indexes is discussed. The authors discus the importance of an adequate surgical treatment especially for liver metastases simultaneously treated to colon cancer. The authors also focus on chemotherapy (FOLFOX and then FOLFIRI) performed in a pre-biological era. Furthermore, the degree to which the HIPEC may have had an impact is still unknown, although it seems to be the gold standard for the treatment of the microscopic peritoneal neoplastic remnant.ConclusionThe authors emphasize that the long term survival in colon cancer with hepatic and ovarian metastases is possible as long as it has an adequate surgical approach, a tailored chemotherapy and an intensive follow-up. Most likely new prognostic markers will have to be identified.     

A Meta-Analysis to Determine the Effect of Primary Tumor Resection for Stage IV Colorectal Cancer with Unresectable Metastases on Patient Survival

Background

Approximately 20 % of patients diagnosed with colorectal cancer will have distant metastases at first presentation (stage IV disease). The effect of removing the primary tumor on survival for patients with stage IV disease with unresectable metastases remains unclear. To address this a meta-analysis of all studies comparing primary tumor resection with chemotherapy alone in cases of stage IV colorectal cancer with unresectable metastases was performed.

Methods

A comprehensive search for published studies examining the effect of primary tumor resection in the setting of colorectal cancer with unresectable metastases was performed. Each study was reviewed and data extracted. Random-effects methods were used to combine data.

Results

There were 21 studies including a total of 44,226 patients that met the inclusion criteria. Resection of the primary tumor in patients with unresectable metastases compared with chemotherapy alone was associated with a lower mortality risk (OR 0.28; 95 % CI 0.165–0.474; P < 0.001), translating into a difference in mean survival of 6.4 months in favor of resection (95 % CI 5.025–7.858, P < 0.001). Patients who underwent resection of the primary tumor were more likely to have liver metastasis only (OR 1.551; 95 % CI 1.247–1.929; P < 0.001), were less likely to have ≥2 metastasis (OR 0.653; 95 % CI 0.508–0.839; P = 0.001), and were less likely to have rectal cancer (OR 0.495; 95 % CI 0.390–0.629; P < 0.001). There was significant cross-study heterogeneity.

Conclusions

Resection of the primary tumor may confer a survival advantage in stage IV colorectal cancer with unresectable metastases but significant selection bias exists in current studies. Randomized controlled trials are essential to validate these findings.     

Optimizing the selection of technically unresectable colorectal liver metastases

BackgroundThe prediction of conversion surgery in patients with technically unresectable colorectal liver metastases has not been generalized or well-established. We developed a predictive model for conversion surgery and assessed the long-term outcomes of patients with technically unresectable colorectal liver metastases.MethodsIn this single-center, retrospective study, we analyzed the perioperative parameters and outcomes of 892 consecutive patients (2014–2021). Conversion surgery was indicated when the chemotherapy response allowed the complete resection of colorectal liver metastases with negative margins and adequate remnant liver volume.ResultsOf the 892 patients, 122 had technically unresectable colorectal liver metastases; 61 underwent conversion surgery (conversion surgery group) and 61 did not (nonconversion surgery group). The median overall survival was significantly higher in the conversion surgery group than in the nonconversion surgery group (5.6 vs 1.8 years, P < .001). After univariate and multivariate analyses, the predictive model for conversion surgery was constructed using 4 predictive factors: Rat sarcoma viral oncogene homolog status (mutant, +2 points), tumor number (≥15, +1), hepatic vein contact (≥2 hepatic veins, +1), and the presence of preservable sections (absence of preservable sections, +2). The area under the curve for conversion surgery was 0.889. Patients were graded according to the scores (A [0–2], B [3–4], and C [5–6]), and the conversion rates were 91.5% (A), 32.6% (B), and 10.3% (C) (P < .001). Grade A patients (median survival time, 5.7 years) had significantly better overall survival than grade B and C patients (median survival time, 2.2 and 1.6 years, respectively; P < .001).ConclusionPatients who underwent conversion surgery for technically unresectable colorectal liver metastases had better prognoses, and our novel predictive model was useful in predicting conversion surgery and prognosis.     

Improved survival after resection of colorectal liver metastases

Background: The goal of this study was to determine if staging with intraoperative ultrasound (IOUS), assessment of porta hepatis lymph nodes, and evaluation of resection margins can improve selection of patients likely to benefit from resection of colorectal liver metastases. Methods: A retrospective evaluation was performed on patients undergoing celiotomy with intent to resect colorectal liver metastases. Patients were considered unresectable if extrahepatic disease was identified by peritoneal exploration or if IOUS demonstated greater than four lesions or the inability to achieve negative margins. Tumor-negative margins were confirmed by pathologic evaluation. Actuarial 5-year survival was calculated using the method of Kaplan and Meier. Results: Median follow-up is 25 months. Of the 151 patients undergoing operative exploration, 107 (71.0%) underwent liver resection (all margins tumor negative). Three operative deaths occurred in this group (2.8%). The disease of 30 patients (19.8%) was considered unresectable due to extrahepatic involvement, and that of 14 patients (9.2%) was demonstrated by IOUS to be unresectable. Five-year actuarial survival was 44% for the resected group and 0% for the unresectable patients (p<0.0001). Conclusions: IOUS, portal node assessment, and pathologic margin evaluation improves the selection of patients likely to benefit from resection of colorectal liver metastases. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Clinical complete response after nivolumab administered as a third-line treatment for unresectable advanced gastric cancer with peritoneal dissemination: A case report

Introduction and importanceNivolumab, which is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has been recommended as a third-line treatment based on the results of the ATTRACTION-2 study involving patients with unresectable advanced gastric cancer.Case presentationA 69 year-old woman was referred to our department with a diagnosis of gastric cancer based on an upper gastrointestinal endoscopy during a medical examination. The endoscopy, along with various tests, helped establish a diagnosis of unresectable advanced gastric cancer (cT4aN3aM1P1c, cStage IV) with peritoneal dissemination. The first and second-line chemotherapy administered was S-1 plus oxaliplatin followed by ramucirumab and nab-paclitaxel, respectively. In this case, the disease was evaluated as progressive disease due to increased peritoneal dissemination. Nivolumab was administered as the third-line treatment. The patient developed interstitial pneumonia after nine courses of nivolumab, for which chemotherapy was discontinued and prednisolone treatment was initiated. The patient had a complete response to treatment endoscopically, 9 months after the last administration of nivolumab. After that, there was no recurrence of the cancer, despite there being no treatment for 5 months.Clinical discussionIt was suggested that the therapeutic effect of nivolumab could be maintained for a long period after discontinuation of its administration. In addition, a correlation has been reported between the treatment efficacy and immune-related adverse events associated with nivolumab.ConclusionsThe synergistic effect of the sustained effect of nivolumab and later-line treatment may contribute to the prolongation of survival after discontinuation of nivolumab in patients who are refractory or intolerant to treatment.     

槐耳颗粒联合FOLFOX4方案治疗结直肠癌的临床观察

目的观察槐耳颗粒联合FOLFOX4化疗方案对结直肠癌患者的生存质量和免疫功能的影响。方法将76例有化疗指征的结直肠癌术后患者随机分成2组,试验组给于槐耳颗粒+FOLFOX4方案,对照组给予安慰剂+FOLFOX4方案。观察2组患者在治疗前后的生存质量、一般状况和免疫状态的改变。结果试验组和对照组治疗有效率分别为92.1%(35/38)和65.8%(25/38),χ2=7.91,P<0.005;生存质量提高率分别为78.9%(30/38)和31.6%(12/38),χ2=6.33,P<0.05;CD3细胞提高率分别为65.8%(25/38)和23.7%(9/38),χ2=7.96,P<0.005;CD4/CD8比值提高率分别为68.4%(26/38)和28.9%(11/38),χ2=10.53,P<0.005。结论槐耳颗粒可显著改善患者症状和生存质量,提高患者免疫状态。槐耳颗粒联合FOLFOX4方案是治疗结直肠癌的一种新的有效方案,值得进一步推广。     

A Randomized Phase II Trial of Three Intensified Chemotherapy Regimens in First-Line Treatment of Colorectal Cancer Patients with Initially Unresectable or Not Optimally Resectable Liver Metastases. The METHEP Trial

Purpose

This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC).

Methods

Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25–30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI-HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS).

Results

A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively.

Conclusions

FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.     

贝伐单抗联合FOLFOX4方案治疗晚期结直肠癌的临床疗效观察

目的观察在直肠癌治疗中联合贝伐单抗及FOLFOX4治疗方案的应用价值。 方法回顾性总结2007年7月至2011年7月期间本院收治的晚期结直肠癌患者87例,按照治疗方案分为试验组(42例)和对照组(45例)。试验组接受贝伐单抗+FOLFOX4方案治疗,对照组只接受FOLFOX4方案治疗,比较两组患者的近期疗效、远期疗效及不良反应。 结果试验组和对照组有效率分别为40.5%和17.8%(χ²=5.466,P<0.05),差异有统计学意义;疾病控制率分别为71.4%和44.4%(χ²=6.472,P<0.05),差异有统计学意义。两组远期疗效比较,试验组2年生存率为85.71%,对照组为66.67%,试验组明显高于对照组(P<0.05)。试验组的中位总生存期和中位无进展生存期分别为15.6和8.9个月,明显优于对照组的10.6和5.8个月,差异均有统计学意义(P<0.05)。两组患者不良反应多为Ⅰ-Ⅱ级,差异无统计学意义。 结论贝伐单抗联合FOLFOX4方案治疗晚期结直肠癌患者效果优于单用FOLFOX4方案治疗,且患者不良反应无明显增加。