Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

Efficacy and tolerance of gemcitabine and nab-paclitaxel in elderly patients with advanced pancreatic ductal adenocarcinoma

BackgroundThe efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting.Patients and methodsWe retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years.ResultsThe study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8–10.2) and PFS (median, 5.5 months; 95% CI, 4.8–6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis.ConclusionGnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.     

Primary esophageal adenosquamous carcinoma: a retrospective analysis of 24 cases

Primary adenosquamous carcinoma (ASC) of the esophagus is a rare kind of malignancy characterized by mixed glandular and squamous differentiation as well as a propensity for aggressive clinical behavior. Data on the evaluation of the clinicopathological features and the prognosis of patients suffering from this malignancy are few because of the rarity of this disease. We conducted a retrospective review of 24 patients with primary esophageal ASC among 6546 esophageal cancer patients who underwent transthoracic esophagectomy in our hospital. The clinicopathological presentation, diagnosis, treatment, and prognostic factors of the patients were respectively investigated. The Kaplan–Meier method and the log rank test were used to calculate and compare overall survival (OS). The Cox proportional hazards model was employed to identify independent prognostic factors. There were 18 males and 6 females with a median age of 60 years (range: 40–78 years). The clinical symptoms, macroscopic type, as well as the radiological and endoscopic features of esophageal ASC were similar to those of esophageal squamous cell carcinoma. Sixteen (88.9%) of the 18 cases who underwent preoperative esophagoscopic biopsy were misdiagnosed as adenocarcinoma or squamous cell carcinoma. The overall median follow‐up period was 36 months, and the median survival time was 32 months. The 1, 3, 5‐year OS rates were 75.0%, 48.5%, and 19.4%, respectively. Univariate analysis showed that gender (P = 0.047), lymph node metastasis (P = 0.007), and TNM stage (P = 0.037) were important factors associated with OS of the 22 patients who underwent radical resection. Multivariate analysis showed that the pathological N stage was the only independent prognostic factor (P = 0.031, hazard ratio [HR], 5.369, 95% confidence interval [CI], 1.167–24.700). These results suggest that esophageal ASC is an uncommon disease prone to be misdiagnosed by endoscopic biopsy. Surgical resection is the primary treatment, but the prognosis of ASC is usually poorer than conventional squamous cell carcinoma. Lymph node metastasis is an independent prognostic factor after radical resection.     

胰腺腺鳞癌9例临床分析

目的：探讨胰腺腺鳞癌临床病理学特点和诊断治疗方法。方法：回顾性分析9例经手术和病理证实的胰腺腺鳞癌的临床、手术及病理资料。结果：本组共9例,77．8％（7／9）为老年患,肿瘤位于胰头6例,胰体尾3例。主要的临床表现是黄疸和腹痛,CT提示胰腺低密度占位。8例获手术切除,1例行胆囊空肠襻式吻合术。病理检查：瘤体平均直径为4．5cm,镜下表现为腺癌和鳞癌混杂。肿瘤侵犯十二指肠3例,侵犯肠系膜上静脉1例,侵犯脾静脉1例,侵犯胃1例,侵犯神经2例,淋巴结转移2例,肝转移1例。随访7例,术后生存3－17月,平均生存时间5．5月,均死于肿瘤复发和肝转移。结论：胰腺腺鳞癌呈侵袭性生长,易侵犯周围脏器和远处转移,恶性程度高,预后差;临床症状和影像学表现无特异性,术前确诊困难;手术切除是有效的治疗手段。     

Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: Results of the PANOVA phase 2 study

Background

Tumor Treating Fields (TTFields), low intensity alternating electric fields with antimitotic activity, have demonstrated survival benefit in patients with glioblastoma. This phase 2 PANOVA study was conducted to examine the combination of TTFields plus chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).

Nal-IRI/5-FU/LV versus modified FOLFIRINOX and FOLFIRI as second-line chemotherapy for unresectable pancreatic cancer: A single center retrospective study

BackgroundThe preferred regimen for unresectable pancreatic cancer following gemcitabine-based chemotherapy is not well-established. This study compared the efficacy of (ⅰ) liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/leucovorin (LV) (nal-IRI/5-FU/LV) versus modified FOLFIRINOX (mFFX) and (ⅱ) nal-IRI/5-FU/LV versus FOLFIRI, respectively, and the safety of the three regimens each other, as second-line chemotherapies for unresectable pancreatic cancer.MethodsThis was a retrospective single-center analysis of all patients who were administered nal-IRI/5-FU/LV, mFFX, or FOLFIRI from December 2014 to July 2021 as second-line chemotherapy for pancreatic cancer. The primary endpoint was the overall survival (OS) of all patients, excluding those with locally advanced pancreatic cancer. Regarding safety, we assessed the incidence of grade ≥3 adverse events of interest in all patients.ResultsA total of 137 patients (nal-IRI/5-FU/LV, n = 55; mFFX, n = 39; FOLFIRI, n = 43) were included. The median OS in the nal-IRI/5-FU/LV group, the mFFX group, and the FOLFIRI group was 7.4, 11.8, and 8.4 months, respectively. Compared with the nal-IRI/5-FU/LV group, the mFFX and FOLFIRI groups displayed a hazard ratio of 0.66 [95% confidence interval 0.40–1.08] and 0.87 [95% confidence interval 0.55–1.39], respectively. In the FOLFIRI group, the incidence of grade ≥3 treatment-related adverse events tended to be low among all three groups.ConclusionsGiven the trend toward longer OS in the mFFX group and the lower incidence of adverse events in the FOLFIRI group, both mFFX and FOLFIRI, as well as nal-IRI/5-FU/LV, can be treatment options for second-line chemotherapy for unresectable pancreatic cancer.     

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy

AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer.METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin(85 mg/m2 in over 120 min) followed by leucovorin(400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan(180 mg/m2 in over 90 min) then 5 fluorouracil(5FU)(400 mg/m2 administred intravenous bolus), followed by 5FU(2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal.RESULTS Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index 10. The most frequent severe toxicities were neutropenia(17 patients, n = 32.7%) and diarrhea(35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients(75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients(48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo(95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor(pancreatic/colorectal) was linked in both analysis.CONCLUSION For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people.     

Contrast-enhanced harmonic endoscopic ultrasonography for predicting the efficacy of first-line gemcitabine and nab-paclitaxel chemotherapy in pancreatic cancer

Background and aimsThe purpose of this study was to assess prognosis with different intratumoral vascularity on contrast-enhanced endoscopic harmonic ultrasonography (CH-EUS) in pancreatic cancer patients receiving chemotherapy.MethodsPatients with unresectable pancreatic cancer who underwent CH-EUS before first-line gemcitabine and nab-paclitaxel (GEM and nab-PTX) therapy were classified into four groups according to vascularity on the early and late phases of contrast enhancement: “Group A″, poor on both phases; “Group B″, rich and poor on the early and late phases, respectively; “Group C″, poor and rich on the early and late phases; “Group D″, rich on both phases. Subgroups were compared in terms of progression-free survival (PFS) and overall survival (OS). We also assessed whether the results with CH-EUS correlate with those of contrast-enhanced computed tomography (CE-CT).ResultsOn CH-EUS, 57, 64, 0, and 24 patients were classified into Groups A, B, C, and D, respectively. The median PFS of patients in groups A, B, and D was 3.9, 7.6, and 10.8 months, respectively, and the median OS were 9.5, 13.1, and 18.6 months, respectively. Both PFS and OS were longest in Group D (p < 0.001 and p < 0.001, respectively). The results of CE-CT were consistent with those of CH-EUS, and there was a correlation between CE-CT and CH-EUS.ConclusionsEvaluation of intratumoral vascularity by CH-EUS may be useful for predicting the efficacy of chemotherapy in patients with pancreatic cancer. A better response to GEM and nab-PTX can be expected in patients showing rich vascularity at both the early and late phases.     

肺腺鳞癌1例报告并文献复习

目的探讨肺腺鳞癌(A SC)的临床表现、病理、影像学特点、治疗和预后。方法回顾性分析一例经病理诊断为肺A SC患者的诊断、治疗、预后特点。结果患者为40岁女性,临床表现为与其它非小细胞肺癌(N SCLC)相比无特殊性。病理特征为光镜下有腺癌和鳞癌两种细胞成分存在。肺影像学表现介于腺癌和鳞癌之间,以周围型肿块伴空洞形成为主要特征。经过积极的多学科治疗,术后生存期12个月,提示肺A SC恶性度高、预后差的特点。结论肺A SC作为N SCLC中独立的亚型,生物学行为和预后有自己的特点,治疗相应具有特殊性。早期诊断,综合治疗是获得长期生存的关键。     

FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan

BackgroundData on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study—a nationwide, multicenter, observational study—FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice.MethodsWe performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings.ResultsOf the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients’ characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2–19.1) months and 6 cycles (range, 1–13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2–13.3), 4.1 (95% CI, 2.6–5.5) months, and 30%, respectively.ConclusionOur findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.     

Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer

AIM: To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency, response, outcome, course of carbohydrate antigen 19-9 (CA 19-9)].METHODS: This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with second-line chemotherapy in our center between 2000 and 2008. All patients received first-line chemotherapy with gemcitabine, and prior surgery or radiotherapy was permitted. We analyzed each chemotherapy protocol for second-line treatment, the number of cycles and the type of combination used. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, response rate, grade 3-4 toxicity, dosage modifications and CA 19-9 course.RESULTS: A total of eighty patients (38%) underwent a second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based regimen. Median number of cycles was 4 (range: 1-12) and the median duration of treatment was 2.6 mo (range: 0.3-7.4). The overall disease control rate was 40.0%. The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI: 4.1-6.6) and 3.4 mo (95% CI: 2.4-4.2), respectively. Toxicity was generally acceptable. Median overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI: 4.5-11.6) vs 5.2 mo (95% CI: 4.0-6.4) for others (P = 0.008).CONCLUSION: A large proportion of patients could benefit from second-line therapy, and CA 19-9 allows efficient treatment monitoring both in first and second-line chemotherapy.     

Humoral hypercalcemia complicating adenosquamous carcinoma of the proximal colon

Summary Hypercalcemia as a complication of carcinoma of the colon is uncommon (1). It usually occurs in the presence of anorectal or rectal carcinoma that metastasizes to the lumbosacral vertebrae (2–4). Hypercalcemia complicating colon carcinoma in the absence of bone metastases—so-called humoral hypercalcemia of malignancy or paraneoplastic hypercalcemia—is rare. Only two such cases associated with adenocarcinoma of the colon (5, 6) and two cases associated with adenosquamous carcinoma of the distal colon (rectum and sigmoid) (7) have been reported. We describe the first reported case of an adenosquamous carcinoma of the cecum and ascending colon that was accompanied by severe humoral hypercalcemia. The hypercalcemia was associated with a parathyroid hormone (PTH) -like substance.     

Choice of first line systemic treatment in pancreatic cancer among national experts

BackgroundTreatment options for patients with metastatic pancreatic cancer depend on various factors, including performance status, tumor burden and patient preferences. Metastatic pancreatic cancer is incurable and many systemic treatment options have been investigated over the past decades. This analysis of patterns of practice was performed to identify decision criteria and their impact on the choice of first-line management of metastatic pancreatic cancer.Materials and methodsMembers of the Swiss Group for Clinical Cancer Research (SAKK) Gastrointestinal Cancer Group were contacted and agreed to participate in this analysis. Decision trees for the first line treatment of metastatic pancreatic cancer from 9 centers in Switzerland were collected and analyzed based on the objective consensus methodology to identify consensus and discrepancies in clinical decision-making.ResultsThe final treatment algorithms included 3 decision criteria (comorbidities, performance status and age) and 5 treatment options: FOLFIRINOX, FOLFOX, gemcitabine + nab-paclitaxel, gemcitabine mono and best supportive care.ConclusionWe identified multiple decision criteria relevant to all participating centers. We found consensus for the treatment of young (age below 65) patients with good performance status with FOLFIRINOX. For patients with increasing age and reducing performance status there was a decreasing trend to use gemcitabine + nab-paclitaxel. Gemcitabine monotherapy was typically offered to patients in the presence of comorbidities. For patients with ECOG 3–4, most of the experts recommended BSC.     

Primary adenosquamous carcinoma of the liver: case report

We describe a case of adenosquamous carcinoma of the liver, including treatment for the recurrence. A 67‐year‐old man with prolonged high fever was diagnosed with a mass lesion in the left lobe of the liver seen by imaging studies. That mass lesion was histologically diagnosed as cholangiocarcinoma by needle biopsy. Left hepatic lobectomy was performed, and a tumor was found that measured 8.0 × 7.0 × 6.0 cm. It was a yellowish white solid mass without macroscopic invasion of the intrahepatic bile duct. Histological examination of the resected specimen revealed both adenocarcinoma and squamous cell carcinoma. The postoperative course was uneventful, but abdominal computed tomography 3 months after operation revealed seven masses in the remnant liver. We diagnosed recurrence of the tumor, and intrahepatic arterial infusion of cisplatin and 5‐fluorouracil was begun. A partial remission resulted. Progression‐free survival after chemotherapy lasted 2 months. However, the tumor markers and remnant tumor size increased gradually 9 months after the operation, and he died 14 months after surgery. We also review 41 cases of adenosquamous carcinoma of the liver reported in the Japanese and English language literature, including the present case.     

肝原发性腺鳞癌6例临床与病理学观察

目的 分析肝原发性腺鳞癌(ASC)患者临床和组织病理学特征。方法 回顾性分析6例肝ASC患者的临床资料,采取肝叶切除或/和经动脉化疗栓塞治疗,采用SP 法检测蛋白表达。 结果 在6例患者中,男性2例,女性4例;年龄为54～75岁,平均年龄为(63.0±8.3)岁;临床均以腹痛为首发表现,影像学检查发现肝内占位性病变;肿瘤组织肉眼观呈灰白色、实性,边界较清晰;镜下见瘤细胞呈巢状或腺管状;6例肝组织腺癌区域均表达CK7、CK19、cam5.2和Ki-67,4例表达CEA,3例表达CK20,2例表达CDX-2,1例表达MUC-1;鳞癌区域均表达p40、p63和CK5/6, 4例弱阳性表达CK19,3例弱阳性表达EMA;术后平均生存6个月。结论 肝原发性腺鳞癌主要依靠病理学检查诊断,其恶性程度较高,患者生存期短。     

Dilemma of first line regimens in metastatic pancreatic adenocarcinoma

Pancreatic cancer is one of the deadliest cancers,ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer(m PC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of m PC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel(GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score(0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness.     

吉西他滨动脉灌注化疗与外周静脉化疗治疗中晚期胰腺癌的比较研究

目的 比较吉西他滨动脉灌注化疗和外周静脉化疗治疗中晚期胰腺癌的临床疗效,旨在评估吉西他滨动脉灌注化疗的有效性和安全性.方法 按照纳入标准,43例中晚期胰腺癌患者被纳入研究,其中21例采用动脉灌注化疗(灌注组),22例采用外周静脉化疗(静脉组),两组均采用吉西他滨为基础联合5-FU化疗.主要评价指标包括l临床受益反应、肿瘤客观缓解率和不良反应.结果 灌注组的临床受益率为8l%,显著高于静脉组的50%(P=0.033);灌注组的疼痛改善率为76.2%,亦显著高于静脉组的45.5%(P=0.039);灌注组的肿瘤客观有效率为33.3%.略高于静脉组的22.7%,相差不显著(P=0.498);两组不良反应无显著性差异.结论 与外周静脉化疗相比,吉西他滨动脉灌注化疗能显著提高中晚期胰腺癌患者的临床受益率,其不良反应轻微,患者耐受性良好.     

Impact of sarcopenia on prediction of progression-free survival and overall survival of patients with pancreatic ductal adenocarcinoma receiving first-line gemcitabine and nab-paclitaxel chemotherapy

Background and aimsSarcopenia is an important prognostic factor for cancer patients. Here, we assessed the effects of sarcopenia on progression-free survival (PFS) and overall survival (OS) of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent treatment with first-line gemcitabine and nab-paclitaxel (GEM and nab-PTX).MethodsThe study enrolled patients with unresectable PDAC who underwent chemotherapy between April 2016 and May 2020. The skeletal muscle index (SMI) at the third lumbar spine level (L3) was calculated from computed tomography (CT) images. Propensity score analysis was used to compare PFS and OS in the sarcopenia and non-sarcopenia groups. Univariate and multivariate analyses were performed to determine variables significantly associated with prognosis.ResultsOf the 176 patients who received first-line GEM and nab-PTX, 84 were selected and divided into two groups of 42 (the sarcopenia and the non-sarcopenia groups) by propensity score matching. The median PFS of the sarcopenia and the non-sarcopenia groups was 5.0 and 8.0 months, respectively (p = 0.004). The median OS was 10.3 and 18.1 months, respectively (p = 0.001). Multivariate analyses revealed that sarcopenia was an independent prognostic factor for PFS and OS (p = 0.004, p = 0.001, respectively). The rates of major grade 3 or 4 AEs were significantly higher in the sarcopenia group (p = 0.008).ConclusionsSarcopenia is an independent indicator of a poor prognosis in patients with PDAC treated with first-line GEM and nab-PTX.     

Efficacy and safety profile of combining agents against epidermal growth factor receptor or vascular endothelium growth factor receptor with gemcitabine-based chemotherapy in patients with advanced pancreatic cancer: A meta-analysis

ObjectivesSeveral clinical trials have been published on gemcitabine-based chemotherapy with or without addition of agents against epidermal growth factor receptor (EGFR) or vascular endothelium growth factor receptor (VEGFR) in patients with advanced pancreatic cancer, however, with diverse results. The objective of this study was to perform a meta-analysis of the published trials.MethodsThe database of CENTRAL, MEDLINE and EMBASE were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated the efficacy and safety profile of adding targeted agents against EGFR or VEGFR to gemcitabine-based chemotherapy in patients with advanced pancreatic cancer. The primary outcome was overall survival (OS) while secondary outcomes included progression free survival (PFS) and overall response rate (ORR). Toxicity profiles were also assessed. Review Manager 5.1 was used to perform the analysis.ResultsResults reported from 6 RCTs involving 2733 patients were included in the analysis. Compared to gemcitabine-based chemotherapy alone, addition of an agent against EGFR resulted in significant longer OS [Hazard ratios (HR) 0.89 (0.79–0.99), p = 0.04] and longer PFS [HR 0.87 (0.79–0.97), p = 0.01], but no significant difference in ORR [RR 1.18 (0.82–1.70), p = 0.36]. The addition of an agent against VEGFR resulted in higher ORR [RR 1.54 (1.03–2.30), p = 0.04], but no advantage in OS [HR 0.95 (0.83–1.09), p = 0.47] or PFS [HR 0.97 (0.77–1.23), p = 0.82].ConclusionsAddition of an agent against EGFR to gemcitabine-based chemotherapy improved OS compared to gemcitabine-based chemotherapy alone in patients with advanced pancreatic cancer, while addition of an agent against VEGFR showed a modest improvement in ORR but not PFS and OS.