Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

Difficult Conversations and Painful Decisions: When Should Patients with Progressive Cancer Stop Chemotherapy?

Introduction: The decision to stop anti-cancer treatment is fraught with many challenges for the oncologist, the patient, and their caregivers. This review examines the special considerations surrounding the decision to cease chemotherapy in terminally ill cancer patient. Methods: A comprehensive literature search was conducted to find relevant publications on chemotherapy cessation. A total of 2700 records were retrieved and 141 were identified as eligible for inclusion in this review. Results: Palliative chemotherapy does not achieve the goal of tumor-related symptom reduction for patients who have experienced progressive disease with more than two prior lines of chemotherapy. ECOG performance status is a crucial predictor of response to therapy and chemotherapy-related complications. Challenges to stopping chemotherapy at the end of life are multifactorial and are both patient and physician-driven. Racial, ethnic, and income-based disparities are seen in the timing and quality of end-of-life conversations offered by physicians to their patients. Conclusions: The decision to cease chemotherapy is one that should be approached with careful consideration and accurate information. Clear communication, compassion and empathy are important components to the therapeutic relationship. Early involvement of palliative care and clear conversations about prognosis and the expected utility of further chemotherapy is essential to conduct the best possible care for cancer patients at the end of life.

Significance of serum carcinoembryonic antigen in metastatic breast cancer patients:A prospective study

BACKGROUND Carcinoembryonic antigen(CEA)is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours.About 36%-70%of breast cancers have elevated serum CEA.And the available studies show discrepancy in addressing the prognostic significance of CEA in advanced breast cancer.AIM To estimate the serum CEA level in our metastatic breast cancer patients and correlate it with response to treatment and clinical outcome.METHODS This was a prospective clinical study conducted on 50 metastatic breast cancer patients treated at breast clinic,with newly diagnosed metastatic breast cancer planned for palliative chemotherapy,targeted therapy,and hormonal treatment.We estimated the proportion of patients with elevated serum CEA level at baseline and after palliative treatment and also studied the association of serum CEA levels with known prognostic factors.The response to treatment was correlated with the serum CEA levels in the context of responders and nonresponders.RESULTS The median pre-treatment and post-treatment CEA levels were 7.9(1.8-40.7)ng/mL and 4.39(1.4-12.15)ng/mL,respectively,in the whole study population(P=0.032).No statistically significant difference was seen in baseline serum CEA between responders and non-responders.Even in the luminal group,pretreatment serum CEA was not a predictor of response,but post-treatment CEA was a significant predictor of tumour progression.In patients with liver and lung metastases,post-treatment CEA level difference was not statistically significant in both responders and non-responders though the values were higher in nonresponders.Among those with bone metastases,69.5%had elevated post-treatment serum CEA,and only 37.5%had elevated serum CEA in those with no bone metastases.CONCLUSION Elevated post-treatment serum CEA levels are associated with disease progression and poor response to therapy.Persistently elevated post-treatment serum CEA levels are significantly associated with bone metastases.Elevated serum CEA and hormonal status are significant predictors of treatment response.

Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture

BACKGROUND Angiogenesis inhibitors(AIs)combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer(CRC).Aflibercept(AFL)is an option for second-line treatment of CRC,according to the‘VELOUR’trial.Currently,we can choose from three AIs,including bevacizumab,ramucirumab,and AFL.Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action.We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.AIM To determine and compare the efficacy and safety profiles of AFL in the secondline and salvage therapy settings.METHODS Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan(FOLFIRI)regimen were collected retrospectively from six institutions in Japan,for the period from May 2017 to March 2019.Patient characteristics collected included age,sex,tumor location,RAS and RAF status,metastatic sites,number of previous treatment cycles,therapeutic response,adverse events,duration of previous AI treatment,and survival time.The end points were time to AFL treatment failure(aTTF)and median survival time post-AFL(aMST).Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting,which was defined as the days since the end of secondline therapy.RESULTS All 41 patients who received AFL+FOLFIRI for advanced CRC had metastatic or unresectable cancer.Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting.The patient characteristics were similar in the two groups,except for two factors.The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients(144 d vs 323 d,P=0.006).In the second-line and salvage therapy groups,the objective response rates were 11%and 0%,respectively(P=0.50),and the disease control rates were 53%and 50%,respectively(P=1.00).In the second-line and salvage therapy groups,the aTTF(123 d vs 71 d,respectively),aMST(673 d vs 396 d,respectively),and incidence of adverse events of grade 3[8(36%)vs 9(47%)]were not significantly different between the two groups.CONCLUSION AFL can be used to treat advanced CRC patients,with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

How to improve metastatic pancreatic ductal adenocarcinoma patients’selection:Between clinical trials and the real-world

As underlined in the minireview by Blomstrand et al,given the poor prognosis and the paucity of data on a therapeutic sequence in pancreatic ductal adenocarcinoma(PDAC),additional randomized controlled trials and real-world evidence studies addressing current and novel regimens are needed.The real-world outcomes of first-line chemotherapy regimens such as FOLFIRINOX and gemcitabine/nab-paclitaxel are thoroughly reviewed and seem to be largely generalizable in a real-world context.Regarding second-line chemotherapy,the key question about the optimal sequence of regimens remains uncertain.Precisely in this setting,it is therefore useful to encourage the implementation of clinical studies that may contribute to the scarcity of data available up to now.We report our experience with a small group of patients treated with second-line liposomal irinotecan(nal-IRI)plus 5-fluorouracil and leucovorin.To improve the treatment of patients affected by PDAC,it is useful to identify subgroups of patients who may benefit from target treatments(e.g.,BRCA mutant)and it is also important to focus on any prognostic factors that may affect the survival and treatment of these patients.

Case Report: A Long Survivor Patient with Stage IV Gastric Adenocarcinoma

Gastric cancer (GC) is the fifth most common malignancy of the world and third leading cause of cancer death. At diagnosis, 35% of GC patients have distant metastases and in these cases the survival rate is very poor with a median overall survival (OS) inferior to 1 year. We report a case of a 67-year-old woman with gastric carcinoma initially deemed limited stage on diagnosis (cT2N0M0), treated surgically with radical subtotal gastrectomy with Billroth II reconstruction. In the staging CT scan, the patient presented a liver image that was considered benign. Three months later, due to abdominal pain, the patient performed another CT scan and the diagnostic of a large single liver metastasis was made;retrospectively it was observed that the lesion was present at diagnosis and that it had increased. A biopsy was performed which confirmed the metastatic origin. In a multidisciplinary team, the lesion was considered unresectable. She was proposed for first line (1st L) palliative chemotherapy (ChT) with FOLFIRI, with partial response as best response. After 30 cycles of FOLFIRI, bone metastases were diagnosed. The patient was submitted to a cementoplasty of D11-12 and L1-2. Afterwards, she started 2nd L ChT with mFOLFOX6 and at the same time she started zoledronic acid every 28 days. The best response to mFOLFOX6 was stable disease. Since November 2018, the patient has been treated with zoledronic acid every 28 days alone and maintains stable disease without ChT.