Phase 1 trial of gemtuzumab ozogamicin in combination with enocitabine and daunorubicin for elderly patients with relapsed or refractory acute myeloid leukemia: Japan Adult Leukemia Study Group (JALSG)-GML208 study

We conducted a phase 1 study of a combination of gemtuzumab ozogamicin (GO) plus conventional chemotherapy in elderly patients (??65?years old) with relapsed or refractory CD33-positive acute myeloid leukemia (AML). Patients received a standard dose of enocitabine (200?mg/m2?×?8?days) and daunorubicin (30?mg/m2?×?days 1?C3) plus an escalating dose of GO (1.5?C5?mg/m2 on day 4). The dose escalation of GO was done according to a standard 3?+?3 design following a modified Fibonacci sequence. No dose-limiting toxicities were observed in three patients (median age, 71) at level 1 (1.5?mg/m2) or in three patients (median age, 73) at level 2 (3?mg/m2). Neither veno-occlusive diseases nor sinusoidal obstructive syndromes were noted at either level. However, as GO was withdrawn from the US market in June 2010, based on a randomized study in newly diagnosed AML, we decided not to proceed to the level 3 (5?mg/m2) in order to avoid possibly more severe adverse effects, and also because all six patients experienced grade 4 myelosuppression, with complete remission in three. This study showed that 3?mg/m2 of GO in combination with enocitabine and daunorubicin may be a recommendable dose for a phase 2 study in Japanese elderly patients with CD33-positive AML. The study was registered at the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (http://www.umin.ac.jp/ctr/) as UMIN000002603.     

Loss of lean body mass affects low bone mineral density in patients with rheumatoid arthritis – results from the TOMORROW study

Objectives: Osteoporosis is one of the complications for patients with rheumatoid arthritis (RA). Rheumatoid cachexia, the loss of lean body mass, is another. However, the relationship between decreased lean body mass and reduced bone mineral density (BMD) in patients with RA has not been well studied.

Methods: This study included 413 participants, comprising 208 patients with RA and 205 age- and sex-matched healthy volunteers. Clinical data, BMD, bone metabolic markers (BMM) and body composition, such as lean body mass and percent fat, were collected. Risk factors for osteoporosis in patients with RA including the relationship BMD and body composition were analyzed.

Results: Patients with RA showed low BMD and high BMM compared with controls. Moreover, lean body mass was lower and percent fat was higher in patients with RA. Lean body mass correlated positively and percent fat negatively with BMD. Lean body mass was a positive and disease duration was a negative independent factor for BMD in multivariate statistical analysis.

Conclusion: BMD and lean body mass were significantly lower in patients with RA compared to healthy controls. Lean body mass correlated positively with BMD and decreased lean body mass and disease duration affected low BMD in patients with RA.

Trial Registration: [UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000003876].     

Probe-based optical fiberscopy for the direct observation of peripheral pulmonary lesions

BackgroundPeripheral pulmonary lesions are rarely observed directly before transbronchial biopsy. This study aimed to characterize the differences between malignant and benign peripheral pulmonary lesions according to the findings of direct observation using probe-based optical fiberscopy.MethodsThirty patients who underwent probe-based optical fiberscopy in combination with bronchoscopy using endobronchial ultrasonography with a guide sheath for the evaluation of peripheral pulmonary lesions were prospectively included in this study. The patients were divided into the malignant and benign groups according to their final diagnosis. The findings of probe-based optical fiberscopy in the two groups were compared.ResultsThe numbers of patients who were diagnosed using histological or bacteriological analyses via bronchoscopic sampling in the malignant and benign groups were 20/23 (87.0%) and 2/7 (28.6%), respectively. On probe-based optical fiberscopy, angiogenesis and vascular engorgement were observed only in the malignant group. The disappearance of subepithelial microvessel transparency and presence of bronchiolar stenosis were observed more frequently in the malignant group (78.3% and 60.9%) than in the benign group (28.6% and 28.6%), whereas increased mucus secretion was observed more frequently in the benign group (71.4%) than in the malignant group (8.7%).ConclusionsThese results suggest that the findings of direct observation using probe-based optical fiberscopy are useful for differentiating malignant from benign peripheral pulmonary lesions.Trial registryUMIN-CTR; UMIN000018796; URL: https://www.umin.ac.jp/ctr/index.htm.     

Modified FOLFIRINOX for resected pancreatic cancer: Opportunities and challenges

Pancreatic cancer is one of the leading causes of cancer death worldwide.Adjuvant chemotherapy has been developed based on the experiences made with palliative chemotherapy, and advocated to improve long-term survival of patients with this disease. However, the optimal chemotherapeutic regimen remains controversial. Recently, Conroy et al demonstrated the impressive benefits of modified FOLFIRINOX over gemcitabine alone in the multicenter Partenariat de Recherche en Oncologie Digestive 24(PRODIGE-24) trial. The remarkable results mark a new milestone in treating resectable pancreatic cancer and have now changed the standard of care for this patient population. In this commentary, we discuss an issue of difference of tumor grade between the PRODIGE-24 trial and previous phase III trials. We also discuss potential biomarkers predicting therapeutic response to modified FOLFIRINOX. Finally,we summarize several ongoing clinical trials of replacing part of the FOLFIRINOX regimen with Xeloda/S-1/nanoliposomal irinotecan for pancreatic cancer.     

Occurrence and disease burden of respiratory syncytial virus and other respiratory pathogens in adults aged ≥65 years in community: A prospective cohort study in Japan

BackgroundThe frequency and clinical profile of respiratory syncytial virus (RSV)–acute respiratory disease (ARD) in older adults in Japan has not been well‐characterized.MethodsThis was a multicenter prospective observational cohort study to evaluate the occurrence rate of ARD in 1000 older adult participants (≥65 years) for 52 weeks during the 2019 to 2020 season. A multiplex polymerase chain reaction panel was used for pathogen detection in nasopharyngeal swab from participants diagnosed with ARD. Symptoms and impact of ARD was assessed using the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™). The study was registered at UMIN (https://www.umin.ac.jp/ctr/): UMIN000037891.ResultsRSV–ARD was detected in 24/1000 (2.4%) participants and RSV‐lower respiratory tract disease in 8/1000 (0.8%) participants. The median duration of RSV–ARD was 18 days. All 24 participants had utilized the medical services of outpatient visits and only 1 (4.2%) participant was hospitalized for RSV–ARD. The most common viruses other than RSV that caused ARD (detected in >10 participants) were human rhinovirus/enterovirus, parainfluenza 3, coronavirus OC43, human metapneumovirus, and influenza A/H1. The most frequent symptoms of RSV–ARD were cough, sore throat, nasal congestion, and expectoration.ConclusionsRSV was reported as a major pathogen for respiratory infections in older adults in Japan.     

晚期胰腺癌内科治疗的研究进展

化疗是目前晚期胰腺癌内科治疗的重要手段.吉西他滨(gemcitabine,GEM)为治疗晚期胰腺癌的一线药物,以其为基础的联合治疗方案在不断探索中,并取得一定进展.FOLFIRINOX方案成为首个经选择患者的、疗效优于GEM的非GEM方案.随着研究的深入,多种靶向药物的出现(包括细胞毒药物或生物靶向药物)给胰腺癌的治疗带来了希望.本文将对胰腺癌的化疗和靶向治疗作一总结,以供临床参考.     

Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer?

Treatment of locally advanced pancreatic cancer is challenging. Despite continuing research, effective treatments continue to be elusive with median survival of only 8-12 months. Treatment options for locally advanced pancreatic cancer include radiation therapy, concurrent chemoradiation or chemotherapy. It is felt that radiation therapy is a suboptimal treatment as most of patients will die of systemic disease. In the past, radiation with 5-FU was the standard treatment for locally advanced pancreatic cancer. But now radiation has been used with combination other chemo agents such as paclitaxel or gemcitabine in order to increase the efficacy. Chemotherapy such as gemcitabine alone or gemcitabine doublet also has been studied in patients with locally advanced pancreatic cancer as well with overall survival being approximately the same magnitude as chemoradiation. The exact role of chemoradiation or chemotherapy in treatment of locally advanced pancreatic cancer is yet to be defined. Hence, this review summarizes and compares of role of radiation, chemoradiation and chemotherapy in treating this disease.     

A phase II study of gemcitabine plus nab-paclitaxel as first-line therapy for locally advanced pancreatic cancer

Gemcitabine plus nab-paclitaxel (GnP) is widely used in clinical practice, despite a lack of prospective data to validate its efficacy in locally advanced pancreatic cancer (LAPC). We conducted a phase II study of GnP for LAPC to assess its efficacy and safety.We performed a single-arm, single-institution study with GnP in 24 patients with LAPC. The treatment protocol included successive administration of gemcitabine (1000 mg/m²) and nab-paclitaxel (125 mg/m²). The primary endpoint was the tumor overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events (AEs).The median PFS was 11.0 months, median OS was 21.2 months, ORR was 62.5%, and 37.5% of the patients had stable disease. Four (16.7%) of the patients were converted to surgical resection; 3 of these achieved R0 resection. Grade 3 to 4 AEs included hematological (neutropenia, 64%; thrombocytopenia, 12%), nonhematological (cholangitis, 16%), and sensory neuropathy (4%). These AEs were manageable and tolerable.The GnP treatment in patients with LAPC showed favorable tumor shrinkage, good toxicity profile, and enabled conversion to surgical resection in a subset of patients; therefore, GnP is an option for first-line chemotherapy in patients with LAPC.     

Improved prognosis of pancreatic cancer patients with peritoneal metastasis

BackgroundPeritoneal metastasis is one of the most important poor prognostic factors in advanced pancreatic cancer (PC). Whether the prognosis of PC with peritoneal metastasis has improved with the advent of gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) is uncertain. The aim of this study was to evaluate the improvements in treatment outcomes of PC with peritoneal metastasis.MethodsWe retrospectively investigated consecutive PC patients with peritoneal metastasis treated with chemotherapy at our institution between 2010 and 2019. We compared the clinical characteristics and survival outcomes according to the period of diagnosis (group A, 2010–2014; group B, 2015–2019) and chemotherapy regimen. We also examined the prognostic factors for overall survival (OS).ResultsAmong 180 patients included (GnP 88; mFFX 14; other regimens 78), distant metastasis was confined to the peritoneum in 89 patients. Although group B had a worse performance status compared to group A, median OS was significantly longer in group B. GnP and mFFX showed a significantly higher objective response rate and disease control rate in addition to longer progression free survival and OS compared to other regimens. The administration of GnP or mFFX, performance status, and neutrophil to lymphocyte ratio ≥5 were identified as independent prognostic factors for OS. Furthermore, the amount of ascites and extent of peritoneal metastasis were significantly associated with OS in patients with distant metastasis confined to the peritoneum.ConclusionsThe prognosis of PC with peritoneal metastasis has significantly improved over time with the advent of GnP and mFFX.     

Medical treatment of pancreatic cancer: new hopes after 10 years of gemcitabine

Exocrine pancreatic cancer has a very poor prognosis. R0 resection of the tumor is to date the only potentially curative approach, but less than 20% of patients are eligible for a curative surgery at diagnosis. Until recently, gemcitabine was the standard treatment for advanced and metastatic pancreatic cancer patients, since it was shown more than a decade ago to induce clinical benefit and to improve survival when compared to weekly bolus 5-fluorouracil. In order to improve patients' outcome many trials have, during the last 10 years, explored the pharmacokinetic modulation of gemcitabine and combination therapies with gemcitabine and other anti-cancer agents with consistent negative results. It is finally a trial assessing the efficacy of a combination chemotherapy without gemcitabine: the FOLFIRINOX regimen, reported this year, that has shown for the first time a significant improvement in progression free and overall survivals. In parallel, many trials testing new targeted agents in these patients are currently ongoing. After 10 years without significant progress in the treatment of pancreatic cancer patients, the hope that a significant improvement in the outcome of these patients can be achieved has been raised.     

Development of chemotherapy and significance of conversion surgery after chemotherapy in unresectable pancreatic cancer

While surgery currently remains the only potentially curative treatment available for pancreatic cancer, only 20% to 30% of patients have resectable disease at diagnosis. Recently, with the introduction of intensive chemotherapy regimens such as oxaliplatin, irinotecan, fluorouracil plus leucovorin (FOLFIRINOX) and gemcitabine plus nab‐paclitaxel, for the treatment of unresectable pancreatic cancer, the antitumor activity and overall survival in patients with pancreatic cancer have dramatically improved. These advances in intensive chemotherapy have led to the possibility of conversion of unresectable disease to resectable disease, and it has been reported that more than 20% of pancreatic cancer patients with unresectable locally advanced disease at diagnosis undergo successful conversion surgery after FOLFIRINOX therapy. In metastatic pancreatic cancer, resection for the primary lesion of pancreatic cancer may show some benefits for some patients with complete resolution of metastases by chemotherapy. Furthermore, surgical resection in some patients with only a few metastases, so‐called oligometastases, have also been reported. Conversion surgery is becoming increasingly possible with the introduction of intensive chemotherapies, however, the actual clinical benefits of resection in such cases has not yet been sufficiently investigated. The long‐term safety, feasibility and outcomes still need to be investigated in well‐designed, multi‐institutional studies on a large number of patients.     

Chest tightness is relieved with the use of asthma drugs except bronchodilators

Objective: Many patients with a chief complaint of chest tightness are examined in medical facilities, and a lack of diagnosis is not uncommon. We have reported that these patients often include those with chest tightness relieved with bronchodilator use (CTRB) and those with chest tightness relieved with the use of asthma drugs except bronchodilators (CTRAEB). The purpose of this study was to demonstrate the clinical characteristics of the patients with CTRAEB and compare them with data from patients with CTRB. Methods: Patients with CTRB (n?=?13) and CTRAEB (n?=?7) underwent a bronchodilator test, assessments of airway responsiveness to methacholine, bronchial biopsy, and bronchial lavage under fiberoptic bronchoscopy before receiving treatment. In all, 10 healthy subjects, 11 bronchial biopsy control patients, and 10 asthmatic patients were recruited for comparison. Results: Inhalation of a short-acting ß₂-agonist (SABA) increased the forced expiratory volume in one second (FEV₁) by 5.1%?±?4.0% in patients with CTRB and by 1.3%?±?3.5% in patients with CTRAEB, and the difference was statistically significant (p?=?0.0449). The bronchial biopsy specimens from the patients with CTRB and CTRAEB exhibited significant increases in T cells (p?<?.05) compared with those of the control subjects. The bronchial responsiveness to methacholine was increased in only a minor portion of patients with CTRB and CTRAEB. Conclusions: We hypothesized that the clinical condition of patients with CTRAEB involves chest tightness arising from inflammation alone, and this chest tightness is mostly associated with airway T cells, without constriction of the airways. There is little to distinguish CTRAEB from CTRB aside from the response to bronchodilator treatment.

This clinical trial is registered at www.umin.ac.jp (UMIN13994, 13998, and 16741).     

Clinical impact of multimodal treatment including chemoradiotherapy,conversion surgery and postoperative chemotherapy for borderline resectable and unresectable locally advanced pancreatic cancer without disease progression after gemcitabine plus nab-paclitaxel

BackgroundThe purpose of this study was to investigate treatment outcomes of chemoradiotherapy (CRT) using S-1 with or without conversion surgery after gemcitabine plus nab-paclitaxel (GnP) for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer.MethodsFrom 2016 to 2020, patients without disease progression after GnP for BR or UR-LA pancreatic cancer underwent CRT with S-1. If distant metastasis was not detected after CRT, conversion surgery and oral administration of S-1 as postoperative adjuvant chemotherapy for at least 6 months was performed.ResultsForty patients were included in the present study. The median number of cycles of GnP was 6. Surgery was performed after CRT in 25 patients. The median progression-free survival (PFS) and overall survival (OS) periods from the start of radiotherapy were 24.6 and 27.4 months, respectively. The OS periods from the start of radiotherapy in patients who underwent conversion surgery and those who did not undergo conversion surgery were 41.3 and 16.8 months, respectively. The PFS periods from the start of radiotherapy in patients who underwent surgery and those who did not undergo surgery were 28.3 and 8.6 months, respectively. Patients who were able to receive S-1 after conversion surgery for more than 6 months had better OS than those who were not (p = 0.039), although there was no significant difference of PFS (p = 0.365).ConclusionsIn BR/UR-LA pancreatic cancer without disease progression after GnP, multimodal treatment including CRT, conversion surgery and the scheduled postoperative chemotherapy may be effective.     

Is there a standard of care for the management of advanced pancreatic cancer?. Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 25-27, 2008

Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, the outcome for this disease remains dismal. Gemcitabine, the standard chemotherapy for pancreatic cancer, offers modest improvement of tumor-related symptoms and marginal advantage of survival. Many chemotherapeutic and targeted agents have been pitted against or combined with gemcitabine in randomized phase III trials and no drug was shown to be superior to single-agent gemcitabine except two gemcitabine-containing combinations: capecitabine plus gemcitabine vs. gemcitabine and erlotinib. In this article, the author debates: "Is there a standard of care for the treatment of advanced pancreatic cancer?". In addition, he summarizes the key studies presented at the "Gastrointestinal Cancers Symposium" held in Orlando, FL, USA on January 25-27, 2008. The studies discussed here include the following: i) a phase I study of a chemotherapy doublet gemcitabine plus capecitabine, combined with a biologic doublet (bevacizumab plus erlotinib) in patients with advanced pancreatic adenocarcinoma (abstract #141); ii) a phase II study of gemcitabine, bevacizumab, and erlotinib in locally advanced and metastatic adenocarcinoma of the pancreas (abstract #151); iii) final results of the multicenter phase II study on gemcitabine, capecitabine, and bevacizumab in patients with advanced pancreatic cancer (abstract #198); iv) interim results from a phase II study of volociximab in combination with gemcitabine in patients with metastatic pancreatic cancer (abstract #142); v) a pilot study of combination chemotherapy with S-1 and irinotecan for advanced pancreatic cancer (abstract #155); vi) a multicenter phase II study of gemcitabine and S-1 combination chemotherapy in patients with unresectable pancreatic cancer (abstract #212); vii) a phase I/II study of PHY906 plus capecitabine in patients with advanced pancreatic carcinoma (abstract #260); and viii) the final results of a phase II trial of Genexol-PM(R), a novel cremophor-free, polymeric micelle formulation of paclitaxel in patients with advanced pancreatic cancer (abstract #269). Based on the results presented at the meeting, it comes to us that patients with locally advanced vs. metastatic pancreatic cancer should be studied separately, better understanding of the biology of pancreatic cancer is mandatory and evaluation of novel agents is crucial. We, as oncologist, have to change our attitudes towards clinical trials and need to think beyond a trial design such as gemcitabine vs. drug of our choice.     

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM：To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS： We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS： Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION： Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.     

Bronchial biopsy and reactivity in patients with chest tightness relieved with bronchodilator

Objective: It has been hypothesized that some patients with chest tightness of unknown origin can be successfully treated with a bronchodilator and that they should be diagnosed with chest pain variant asthma. We conducted a prospective study to characterize newly diagnosed patients with chest tightness relieved with bronchodilator use and without characteristic bronchial asthma attacks. Methods: Eleven patients were registered following recurrent positive responses of chest tightness to inhalation of a ß₂-agonist. These patients underwent assessments of airway responsiveness to methacholine, bronchial biopsy and bronchial lavage under fiber-optic bronchoscopy before receiving treatment. Results: For the patients with chest tightness relieved with bronchodilator use, the bronchial biopsy specimens exhibited significant increases in lymphocyte and macrophage infiltration (p < 0.05) and no significant increase in eosinophils (p = 0.2918) compared with the control subjects. The bronchial responsiveness to methacholine was increased in two of the patients with chest tightness, and it was not increased in seven; in addition, increased percentages of eosinophils were detected in bronchial lavage fluid (5% or more) from two patients, but no increase was detected in eight patients. Conclusions: We suspect that the chest tightness was induced by airway constriction in these patients, but further study is necessary to validate this hypothesis. We propose that the chest tightness relieved with bronchodilator use was attributed to airway constriction resulting from inflammation with lymphocytes and macrophages and/or that the chest tightness was directly attributed to airway inflammation. This clinical trial is registered at www.umin.ac.jp (UMIN13994 and UMIN 16741).     

Pancreatic Cancer Registry in Japan: 20 years of experience

The prognosis of pancreatic cancer is defined by the histology and extent of disease. Preoperative histologic diagnosis and diagnostic imaging are fundamentals in managing the disease, but it is not rare to find unexpected peritoneal dissemination or liver metastasis at the time of operation. The overall resectability rate of pancreatic cancer is 40% in Japan. Resecting the portal vein and peripancreatic plexus were performed on 40% of the patients who underwent pancreatectomy for invasive cancer in the head of the pancreas. Long-term survival was only found in patients who underwent pancreatectomy. Radical lymph node dissection, or combined resection of the large vessels, did not seem to improve survival further than the standard resection. Multidisciplinary treatments combined with surgery were performed, and various effects of postoperative chemotherapy after pancreatectomy, intraoperative- and postoperative-radiation therapy, or postoperative chemotherapy for unresectable tumor, were shown. Development of unconventional therapies and refinement of the conventional therapy should be promoted on a randomized prospective trial basis. To promote this effort, which requires the international comparisons and cooperation, JPS developed a computerized JPS registration system downloadable from the JPS website (http://www.kojin.or.jp/suizou/index.html).     

A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study

We conducted a prospective randomized study to assess the optimal postremission therapy for adult acute myeloid leukemia in patients younger than 65 years in the first complete remission. A total of 781 patients in complete remission were randomly assigned to receive consolidation chemotherapy of either 3 courses of high-dose cytarabine (HiDAC, 2 g/m(2) twice daily for 5 days) alone or 4 courses of conventional standard-dose multiagent chemotherapy (CT) established in the previous JALSG AML97 study. Five-year disease-free survival was 43% for the HiDAC group and 39% for the multiagent CT group (P = .724), and 5-year overall survival was 58% and 56%, respectively (P = .954). Among the favorable cytogenetic risk group (n = 218), 5-year disease-free survival was 57% for HiDAC and 39% for multiagent CT (P = .050), and 5-year overall survival was 75% and 66%, respectively (P = .174). In the HiDAC group, the nadir of leukocyte counts was lower, and the duration of leukocyte less than 1.0 × 10(9)/L longer, and the frequency of documented infections higher. The present study demonstrated that the multiagent CT regimen is as effective as our HiDAC regimen for consolidation. Our HiDAC regimen resulted in a beneficial effect on disease-free survival only in the favorable cytogenetic leukemia group. This trial was registered at www.umin.ac.jp/ctr/ as #C000000157.     

FOLFIRINOX-based neoadjuvant chemoradiotherapy for borderline and locally advanced pancreatic cancer: A pilot study from a tertiary centre

BackgroundNeoadjuvant chemoradiotherapy, potentially relevant to increase resection rate in pancreatic cancer, is still debated.AimsTo assess tolerance, resection rate and outcomes of patients with non-metastatic pancreatic ductal adenocarcinoma treated by concomitant chemoradiotherapy.MethodsThis monocentric study included all consecutive patients treated from 2010 to 2014 for non-metastatic pancreatic adenocarcinoma. Chemotherapy was followed by chemoradiotherapy in operable patients, surgical resectability being assessed by CT-scan.ResultsSeventy-nine patients were included: 41 patients had borderline and 38 locally advanced tumours. All patients were treated by chemotherapy (FOLFIRINOX), followed by chemoradiotherapy (median dose: 59 Gy, range 45–66 Gy) for 94% of patients. Thirty-seven patients (47%) could subsequently benefit from surgery with a complete R0 resection in 94% of cases, with a postoperative mortality of 5%. Median overall survival was 21.5 months (median follow-up: 48.8 months). Local control, overall and disease-free survival were significantly higher for patients who underwent resection compared to others, with 89.2% vs 59.5% (p = 0.01), 49.7 vs 17.4 months (p < 0.01) and 25.5 vs 9.2 months (p < 0.01), respectively.ConclusionNeoadjuvant treatment consisting of FOLFIRINOX chemotherapy followed by chemoradiotherapy is an efficient strategy for patients with borderline and locally advanced pancreatic cancer, resulting in a 43% rate of secondary complete surgical resection associated with high local control, overall and disease-free survival.     

Chemotherapy for pancreatic cancer]

Chemotherapy is expected to play an important role in the treatment of pancreatic cancer because most of pancreatic cancers are being discovered at locally advanced or metastatic stages and recurrence rate is high even after the curative resection. Gemcitabine is a key agent for the first-line therapy of advanced pancreatic cancer. It can enhance the quality of life and prolong the survival of patients. Combination of erlotinib or capecitabine with gemcitabine showed a marginal survival benefit over single-agent gemcitabine. If patient's performance state is good, gemcitabine-based platinum combination therapy showed overall survival benefit compared with gemcitabine monothrapy. If the first-line palliative chemotherapy fails, 5-FU, capcitabine, or tegafur with or without combination can be used as the second-line agents. Adjuvant chemotherapy using 5-FU or gemcitabine after curative resection has overall survival benefit. However, neoadjuvant chemotherapy has not been proven to be effective in the treatment of pancreatic cancer.