Pancreatic adenocarcinoma third line systemic treatments: a retrospective cohort study.

BACKGROUND: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan - Oxaliplatine) and Gemcitabine - Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy. METHODS: A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model. RESULTS: In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn't influence 3rd line outcome. CONCLUSION: In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.

Pancreatic cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up

The opportunity to detect pancreatic cancer (PC) when potentially curable depends on early diagnosis and an ability to identify and screen high-risk populations before symptoms arise. Identification of a high-risk population is challenging and optimal screening tools remain unclear.1 Older age is the strongest risk factor; incidence peaks at 65-69 years in males and 75-79 years in females.2 A pooled analysis of 117 meta-analyses assigned a relative risk to a number of common risk factors (Supplementary Table S1, available at https://doi.org/10.1016/j.annonc.2023.08.009).3 The vast majority (>80%) of PCs arise due to sporadically occurring somatic mutations. Only a small proportion are due to inherited deleterious germline mutations.1 Familial PC, defined as at least two first-degree relatives with PC, accounts for only 4%-10% of all cases. Variants in BRCA2 are the most common genetic abnormalities seen in familial PC. Other familial syndromes linked to PC are listed in Supplementary Table S2, available at https://doi.org/10.1016/j.annonc.2023.08.009. Individuals from families at risk should receive genetic counselling and be considered for enrolment in investigational screening registries. Currently, in high-risk individuals, annual endoscopic ultrasound (EUS) and/or pancreatic magnetic resonance imaging (MRI) are the procedures of choice for surveillance.4 Surveillance programmes usually begin at age 50 years (or 10 years earlier than the age of the youngest affected relative). Prospective surveillance data in high-risk individuals demonstrated high rates of resectability and encouraging observations of long-term survival.5, 6, 7, 8, 9 In sporadic PC, the major risk factors are tobacco, Helicobacter pylori infection and factors related to dietary habits (high red meat, high alcohol intake, low fruit and vegetable intake, overweight/obesity and type 2 diabetes mellitus).2,3,10 Chronic pancreatitis, irrespective of the cause (alcohol abuse, smoking, genetic mutations), is a risk factor for PC. A proportion of the risk factors associated with PC are potentially modifiable, affording a unique opportunity for primary prevention that is yet to be realised.

The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

Efficacy and tolerance of cetuximab in combination with 5 FU plus irinotecan based chemotherapy in metastatic squamous cell anal carcinoma.

BACKGROUND: Squamous cell anal carcinoma (SCAC) is an uncommon neoplasia often cured by surgery and/or chemo-adiation therapy at the localized stage. Although the first-line treatment for metastatic anal canal cancer is now better codified with two validated treatment regimens, carboplatin-paclitaxel and modified docetaxel-cisplatin-5FU (DCF), there is little data and no consensus regarding subsequent lines [1-5]. In this study, we report the safety and efficacy of cetuximab (an epidermal growth factor receptor inhibitor) in combination with 5-FU plus irinotecan based chemotherapy. METHOD: A retrospective analysis of patients with metastatic SCAC (mSCAC), who failed on at least one prior line of treatment, before being treated with the combination FOLFIRI and cetuximab between March 2015 and February 2022 at Gustave Roussy cancer center, was performed. RESULTS: A total of 33 patients with a pre-treated mSCAC were analyzed. The combination of FOLFIRI and cetuximab provided a disease control rate (DCR) of 73%, and response rate of 30%. With a median follow-up of 38 months, the median progression free survival was 5.5 months, and the median overall survival was 13.7 months. Fourteen patients (42%) experienced grade III/IV adverse events that remained manageable. CONCLUSION: Our study suggests that FOLFIRI and cetuximab is a promising combination in the management of mSCAC with a very good DCR and a manageable toxicity profile. Further prospective trials would be needed to confirm our results.

MODUL cohort 2: an adaptable, randomized, signal-seeking trial of fluoropyrimidine plus bevacizumab with or without atezolizumab maintenance therapy for BRAFwt metastatic colorectal cancer.

BACKGROUND: MODUL is an adaptable, signal-seeking trial designed to test novel agents in predefined patient subgroups in first-line metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with measurable, unresectable, previously untreated mCRC received induction with ≤8 cycles of FOLFOX + bevacizumab followed by randomization to maintenance treatment comprising control [fluoropyrimidine (FP)/bevacizumab: 5-fluorouracil 1600-2400 mg/m2 46-h intravenous (i.v.) infusion day 1 q2 weeks plus leucovorin 400 mg/m2 2-h infusion i.v. day 1 q2 weeks or capecitabine 1000 mg/m2 b.i.d. orally days 1-14 every 21 days; bevacizumab 5 mg/kg 15-30-min i.v. infusion q2 weeks] or experimental treatment in one of four biomarker-driven cohorts. In patients with BRAF wild-type (BRAFwt) tumors (cohort 2), experimental treatment was FP/bevacizumab + atezolizumab (800 mg 60-min i.v. infusion q2 weeks). Primary efficacy endpoint was progression-free survival (PFS; intent-to-treat population). Enrollment is complete; efficacy and safety findings from cohort 2 are presented. RESULTS: Four hundred and forty-five patients with BRAFwt mCRC were randomized (2 : 1) to maintenance in cohort 2. At a median follow-up of 10.5 months, PFS outcome hypothesis was not met [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.72-1.17; P = 0.48]; overall survival (OS) was immature. At a median follow-up of 20.3 months (2-year survival follow-up), PFS benefit was also not met (HR 0.95; 95% CI 0.77-1.18; P = 0.666); OS HR with nearly two-thirds of patients with events was 0.83 (95% CI 0.65-1.05; P = 0.117). No new safety signals were identified. The most common grade ≥3 treatment-emergent adverse events (TEAEs) for experimental versus control arms were hypertension (6.1% versus 4.2%), diarrhea (3.1% versus 2.1%), and palmar-plantar erythrodysesthesia syndrome (1.0% versus 2.5%). Four patients experienced TEAEs with fatal outcome, two were study treatment-related: hepatic failure (experimental arm) and large intestine perforation (control arm; bevacizumab-related). CONCLUSIONS: Adding atezolizumab to FP/bevacizumab as first-line maintenance treatment after FOLFOX + bevacizumab induction for BRAFwt mCRC did not improve efficacy outcomes.

Lung carcinoids with high proliferative activity: Further support for the identification of a new tumor category in the classification of lung neuroendocrine neoplasms.

Highly proliferative lung carcinoids (HPLC) have been recently reported but information about this subset remains scarce. OBJECTIVES: Clinical and pathological data of 630 patients with lung carcinoids (LC) referred to Gustave Roussy Institute (GR) and European Institute of Oncology (IEO) were retrospectively reviewed to select HPLC and analyze their frequency, behavior and compare their outcome to conventional LC with Ki-67 ≤ 20 % and mitotic count (MC)≤10/2 mm2. MATERIALS AND METHODS: Selection criteria were: diagnosis of LC confirmed by local pathologist, and available clinical and follow-up data. Patients with Ki-67 > 20 % and/or MC > 10/ 2 mm2 in primary or metastatic specimens were identified as HPLC. RESULTS: 30/514 patients (6%) met the selection criteria of HPLC. Based on primary tumor evaluation, 22/25 (88 %) were classified as atypical carcinoids (AC). Median MC was 4.5/2 mm2 (1-11) 6/2 mm2 (3-15) in primary tumors and metastasis, respectively. Median Ki-67 was respectively 23 % (15-65) and 25 % (8-60). Recurrence rate was 66 % (12/18) in HPLC and 9 % (33/352) in conventional LC. Median RFS was 24 (10-NR) months in HPLC, 288 (141-NR) months in LC with Ki-67 index≤5 % and NR (148-NR) months in LC with Ki-67 6-20% (p < 001). Median OS was 203 (83-NR) months in LC with Ki-67 index≤5%, 101 (79-NR) months in LC with Ki-67 index 6-20 % and 53 (39-NR) months in HPLC (p = 002). Among 20 metastatic patients with HPLC, median PFS under platinum-based chemotherapy, everolimus, alkylating-based chemotherapy, FOLFOX and PRRT was 5.1 (95 % CI 0.7-9.4), 12.1(95 %CI 0.3-24), 6.8 (95 % CI 0-14.9), 10.2 (95 % CI 0.4-19.9) and 14.2 months (95 % CI 0-30) respectively. Best response was stable disease (SD) under platinum-based chemotherapy and partial response (PR) under alkylating-based chemotherapy and FOLFOX. CONCLUSION: This study confirms the existence and rarity of HPLC. Their characteristics and clinical behavior are more similar to LC rather than neuroendocrine carcinomas (NECs), suggesting that this entity could be managed accordingly.

Is intra-arterial hepatic chemotherapy painful?

BACKGROUND: Liver metastases are mainly supplied by the hepatic artery, allowing the administration of intra-arterial hepatic chemotherapy (IAHC) while preserving normal parenchyma. The progression-free survival and response rate are prolonged by IAHC which can improve the rate of secondary resectability. Severe abdominal pain requiring high-dose opioids can appear during HIAC administration. This pain is related to extrahepatic infusion and gastroduodenal ulceration. However, intense abdominal pain was observed under oxaliplatin IAHC specifically without any extrahepatic infusion. METHOD: We retrospectively reviewed the charts of 68 patients who received IAHC in our center between 2011 and 2015. Patient's demographics and disease characteristics were collected. Other variables such as the type, duration, and dosage of the chemotherapy administered, as well as the usage of painkillers before, during, or after intra-arterial administration, were also registered. RESULTS: The mean age of the patients was 59 years. 61.7% were male (n = 42). The mean dose of oxaliplatin administered was 162 mg per cure over 6.7-h course. Fifty percent were diagnosed with a left colon cancer, and 85.2% had synchronous liver metastasis. While 47% of patients received IAHC as a third-line therapy, the main chemotherapeutic drug was oxaliplatin (85.2% of cases; n = 58), then OPTILIV protocol (5FU, irinotecan, oxaliplatin) (13.3%; n = 9), and mitomycin C (1.5%; n = 1). A dose reduction of 23.6% had been noted in 58.8% (n = 40) cases due to adverse effects. Among patients who received opioids during IAHC (n = 40), 20% required opioids in intercure. Before, during, and after IAHC administration, patients complained of abdominal pain in 8.8%, 58.8%, and 19.1%, and opioids were used in 10.2%, 57.3%, and 19.1%, respectively. The main onset of pain occurs during the third cycle of chemotherapy. Among our patients, 11.7% and 22% had ulcer and extrahepatic perfusion, respectively, while 7.3% of them were asymptomatic. The mean occurrence of these signs was during the fourth cycle of IAHC. 33.8% and 52.9% of patients had abdominal pain while an extended and short infusion time, respectively. CONCLUSION: Lengthening of the infusion time did not prevent the occurrence of abdominal pain significantly but was nonetheless decreased compared with patients undergoing short infusion durations. Pain was more common in patients who did not have a dose reduction and who presented with ulcer and extrahepatic perfusion. Abdominal pain occurred on average one cycle before ulcer or extrahepatic perfusion diagnosis. In current practice, pain should be an alarming indicator in patients receiving IAHC, as it may be associated with ulcer or extrahepatic perfusion and thus requiring opioids.

Gender medicine and oncology: report and consensus of an ESMO workshop.

BACKGROUND: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018. DESIGN: Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here. RESULTS: Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy. CONCLUSION: Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.

Management of colorectal peritoneal metastases: Expert opinion.

When peritoneal metastases are diagnosed (strong agreement of experts): (i) seek advice from a multidisciplinary coordination meeting (MCM) with large experience in peritoneal disease (e.g. BIG RENAPE network); (ii) transfer (or not) the patient to a referral center with experience in hyperthermic intraperitoneal chemotherapy (HIPEC), according to the advice of the MCM. With regard to systemic chemotherapy (strong agreement of experts): (i) it should be performed both before and after surgery, (ii) for no longer than 6 months; (iii) without postoperative anti-angiogenetic drugs. With regard to cytoreductive surgery (strong agreement of experts): (i) Radical surgery requires a xiphopubic midline incision; (ii) no cytoreductive surgery via laparoscopy. With regard to HIPEC: HIPEC can be proposed for trials outside an HIPEC referral center (weak agreement between experts): (i) if surgery is radical; (ii) if the expected morbidity is "reasonable"; (iii) if the indication for HIPEC was suggested by a MCM, and; (iv) mitomycin is preferred to oxaliplatin (which cannot be recommended) for this indication.

Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

Background: [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. Patients and methods: In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Results: Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13 €, P < 0.033). Conclusion: 18FDG-PET/CT, when added every 6 months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect. ClinicalTrials.gov identifier: NCT00624260.

Organoids as preclinical models to improve intraperitoneal chemotherapy effectiveness for colorectal cancer patients with peritoneal metastases: Preclinical models to improve HIPEC.

BACKGROUND: Peritoneal metastases (PM), corresponding to tumor implants into the peritoneal cavity, are associated with impaired prognosis and low responsiveness to systemic chemotherapy. A new therapeutic approach has dramatically changed the prognosis of patients with PM from colorectal cancer (CRC), consisting in the association of a complete cytoreductive surgery followed by intraperitoneal chemotherapy associated to hyperthermia (HIPEC). Many drugs have been administered intraperitoneally, but no clear consensus has been approved. Therefore, relevant preclinical models are essentials for the efficient translation of treatments option into affected patients. METHOD: Organoids, the last generation of preclinical models, were used to rationalize and improve intraperitoneal chemotherapy. We tested several cytotoxics, combination, effect of hyperthermia, exposure duration and frequency. RESULTS: Organoids were a representative model of response to chemotherapies used for the treatment of PM from CRC; 460mg/m2 of oxaliplatin being the most efficient cytotoxic treatment. Repeated incubations with oxaliplatin; mimicking cycles of intraperitoneal treatment, resulted in an increased efficacy. CONCLUSION & DISCUSSION: Organoids are relevant models to study the chemosensitivity of peritoneal metastases from CRCs. These models could be used for large scale drug screening strategies or personalized medicine, for colorectal carcinoma but also for PM from other origins.

Long-term survival after aggressive treatment of relapsed serosal or distant pseudomyxoma peritonei.

INTRODUCTION: Complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have dramatically changed the prognosis of patients with pseudomyxoma peritonei (PMP). However, recurrences can still occur and no consensus has been reached regarding their optimal treatments. This study aimed to analyze the patterns of recurrence after CCRS plus HIPEC for PMP and potential subsequent treatments of these lesions. PATIENTS AND METHODS: Between 1992 and 2014, patients who had relapsed after treatment of PMP were selected from a prospective database of 251 patients who had undergone CCRS plus HIPEC with a curative intent. RESULTS: After a median follow-up of 85 months, 66 patients (26%) had relapsed with a median free interval of 25 months. The first recurrence was mostly located in the peritoneum, isolated in 50 patients (76%) and associated with extraperitoneal disease in 6 patients. Curatively intended treatment of the relapse, combining surgery and chemotherapy was achievable in 76% of the patients, leading to a 5-year overall survival (OS) rate of 83% from the date of treatment of the first recurrence. In contrast, the 5-year OS rate was only 27% (p < 0.001) for patients treated with non-curative therapy. An isolated peritoneal recurrence was predictive of greater amenability to curative therapy and a better prognosis. CONCLUSION: After CCRS plus HIPEC, serosal recurrences were more common than their distant counterparts. Distant relapses' emergence has raised the question of their optimal treatments. Very long-term survival can be obtained after further treatment of recurrent PMP for patients with limited disease and good general status.

Imaging of neuroendocrine tumors of the pancreas.

Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan®) is still the most available technique. Gallium 68-SST analogue PET have been demonstrated to be more sensitive than SRS-SPEC and it will be the future of functional imaging for NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined either by negative SRS and huge tumor burden or ki67 above 10% or poorly differentiated PNEC tumors.

The multidisciplinary management of gastro-oesophageal junction tumours: European Society of Digestive Oncology (ESDO): Expert discussion and report from the 16th ESMO World Congress on Gastrointestinal Cancer, Barcelona.

BACKGROUND AND SCOPE: The management of GOJ cancers remains controversial and may vary between countries. Evidence-based attitudes and guidelines are not easy to elaborate since most of the trials and studies reported mixed cases of oesophageal (both adenocarcinoma and squamous cell tumours), GOJ and gastric cancers. The aim of this expert discussion and position paper is to elaborate practical recommendations that integrate evidence-reported literature and experience-based attitude covering all clinical aspects of GOJ cancer across different specialities and countries in Europe. METHODOLOGY: Opinion leaders, selected on scientific merit were asked to answer to a prepared set of questions covering the approach of GOJ tumours from definition to therapeutic strategies. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine. RESULTS: Definition, classification, diagnosis and staging of GOJ tumours were updated and debated. Therapeutic aspects including endoscopic therapy, surgical management, both multimodal curative and palliative management were also reviewed for proposing practical and consensual positions and recommendations whenever possible. CONCLUSION: GOJ tumours deserve specific attention,not only for uniformising clinical management across countries but also for performing specific clinical and translational research,mainly in the curative perioperative setting.

ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.

Evaluation of the combination of oxaliplatin and 5-fluorouracil or gemcitabine in patients with sporadic metastatic pulmonary carcinoid tumors.

OBJECTIVES: The aim of this retrospective study was to analyse the efficacy of gemcitabine-oxaliplatin (gemox) or 5-fluorouracil-oxaliplatin (folfox) in the treatment of metastatic pulmonary carcinoid tumors. PATIENTS AND METHODS: 45 patients were included in two tertiary referral centers between January 1999 and January 2013. Typical, atypical carcinoids or not otherwise specified carcinoids were diagnosed according to WHO criteria in 19%, 57%, and 24% of cases by two expert pathologists. Patients had synchronous (38%) or metachronous (62%) metastastic disease (median of 2 (1-5) metastatic sites). Seventy-nine percent had progressive disease before start of chemotherapy. Treatment consisted of: gemcitabine 1000mg/m(2) and oxaliplatin 100mg/m(2) every 2 weeks (gemox regimen, n=24) or 5-fluorouracil (5-FU) (400mg/m(2) in bolus injection and 5-FU 2400mg/m(2) in 46h-infusion) and oxaliplatin 85mg/m(2) (folfox regimen, n=21) every 2 weeks. Tumor response was assessed according to RECIST criteria every 8-12 weeks. Progression free survival and overall survival were assessed using Kaplan Meier curves. RESULTS: Patients received oxaliplatin-based chemotherapy in first-line (20%), second-line (33%), or post-second-line (47%) systemic treatment. The median number of cycles was 8 (1-12). Nine (20%) stopped oxaliplatin before 8 cycles because of toxicity. Nine patients (20%) had a partial response and 29 (64%) had stable disease. Median progression free survival (PFS) was 15 (6-25) months. Median overall survival (OS) was 34 (21-49) months. No significant difference was observed in response and PFS between either regimens. CONCLUSIONS: Our results suggest that either gemcitabine-oxaliplatin or 5-fluorouracil-oxaliplatin combinations are attractive chemotherapy regimen in metastatic pulmonary carcinoid tumors.