Maintenance Gemcitabine Research Articles

A durable response to gemcitabine monotherapy in metastatic cardiac angiosarcoma

Introduction: Primary cardiac angiosarcoma is a rare neoplasm with high rates of local recurrence and distant metastasis for which optimum treatment is poorly defined. Case Report: We present the case of a 49-year-old man with cardiac angiosarcoma with distant metastases who exhibits durable response to gemcitabine monotherapy. At initial diagnosis, he underwent complete resection with adjuvant Adriamycin and Ifosfamide for four cycles as well as external beam radiation for possible residual disease. He had recurrence with liver and bone metastases four years later. He received Gemcitabine and Docetaxel for six cycles followed by Gemcitabine monotherapy with no evidence of recurrence for the next three years. Conclusion: This patient’s consistent response to gemcitabine maintenance therapy in metastatic cardiac angiosarcoma adds to relative paucity of data regarding the management of this rare malignancy, offering insight into best practice and hope for patients afflicted with this disease.

Assessment of Outcomes of Maintenance Gemcitabine after Standard Chemotherapy in Metastatic Bladder Transitional Cell Carcinoma Patients

Assessment of Outcomes of Maintenance Gemcitabine after Standard Chemotherapy in Metastatic Bladder Transitional Cell Carcinoma Patients

A multicenter, randomized, double-blind phase III clinical study to evaluate the efficacy and safety of KN046 combined with nab-paclitaxel and gemcitabine versus placebo combined with nab-paclitaxel and gemcitabine in patients with advanced pancreatic cancer (ENREACH-PDAC-01).

TPS4189 Background: Pancreatic cancer is biologically aggressive, and the majority of pts was diagnosed as locally advanced or metastatic disease. Nab-paclitaxel and gemcitabine is a frequently used regimen for advanced pancreatic cancer, but chemoresistance is unavoidable. The combination of immunotherapy with chemotherapy have shown efficacy for certain types of cancer, but no similar results have been obtained in pancreatic cancer. KN046, a novel recombinant humanized bispecific antibody, can simultaneously block PD-1/PD-L1 and CTLA-4 pathways and restore T-cell immune response to tumor. In a phase Ⅱ clinical trial (NCT04324307), as of August 10, 2021, 53 pts with unresectable advanced pancreatic cancer had received one cycle KN046 combined AG regimen treatment and 31 subjects had received post-baseline tumor assessment at least once. Objective response rate (ORR) was 45.2% (95% CI: 27.3%, 64.0%) and disease control rate (DCR) was 93.5% (95% CI: 78.6%, 99.2%)，excellent preliminary results have been achieved. Based on this, a phase III pivotal study (ENREACH-PDAC-01) is conducting now in China to verify the efficacy and safety of KN046 plus nab-paclitaxel and gemcitabine as first-line treatment for advanced pancreatic cancer (NCT05149326). Methods: This nationwide multicenter phase III clinical trial enrolled pts with histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic ductal adenocarcinomas with a WHO performance score of 0 or 1 and expected survival period of more than 3 months. Eligible pts will be randomized 1:1 to intervention group or control group and receive 4-6 cycles of KN046 (5mpk Q2W) or placebo combined with nab-paclitaxel (initial dose: 125mg/m2 D1,8,15 Q4W) and gemcitabine (initial dose: 1000mg/m2 D1,8,15 Q4W) followed by KN046 (5mpk Q2W) or placebo with gemcitabine（QW × 3, 1 week off） maintenance therapy. Treatment will continue until disease progression or intolerable toxicity, withdrawal of consent, loss to follow-up or death, end of study, whichever occurs first. The primary endpoint is overall survival (OS). Key secondary endpoints are ORR and progression free survival (PFS). PFS and ORR will be assessed independently per RECIST v1.1 at screening, every 8 weeks for 1 year and then every 12 weeks until disease progression. Tumor and blood samples will be collected at baseline and during study treatment for pharmacokinetic, immunogenicity and biomarker assessment. The first patient was enrolled in early February 2022. Clinical trial information: NCT05149326.

Cetuximab, gemcitabine and radiotherapy in locally advanced pancreatic cancer: Long-term results of the randomized controlled phase II PARC trial

PurposeAddressing the epidermal growth factor receptor (EGFR)-pathway by the competitive receptor ligand cetuximab is a promising strategy in pancreatic cancer. In the prospective randomized controlled phase II PARC-study (PARC: Pancreatic cancer treatment with radiotherapy (RT) and cetuximab), we evaluated safety and efficacy of a trimodal treatment scheme consisting of cetuximab, gemcitabine and RT in locally advanced pancreatic cancer (LAPC). MethodsBetween January 2005 and April 2007, 68 patients with inoperable pancreatic ductal adenocarcinoma were randomized in either trimodal therapy followed by gemcitabine maintenance (Arm A) or in trimodal therapy followed by gemcitabine plus cetuximab maintenance (Arm B). Intensity-modulated RT (IMRT) was performed with a total dose of 45 Gy in 25 fractions and with a simultaneous integrated boost to the gross tumor (54 Gy). Within the trimodal therapy, gemcitabine and cetuximab were administered weekly. Maintenance therapy consisted of gemcitabine only or gemcitabine plus cetuximab. Toxicity, overall survival (OS), secondary resection rate, local control and progression free survival (PFS) were evaluated. ResultsWith a median followup time of 13 months (range: 2 – 184 months), one patient is still alive and one patient is lost to follow-up. Nausea and gastrointestinal hemorrhage were the most important higher-graded (>°II) acute and late non-hematological toxicity (13% and 7%). Median OS was 13.1 months without significant difference between both treatment arms (Arm A: 11.9 months; Arm B: 14.2 months). Compared to historical data, cetuximab did not improve OS. One- and two-year local control rates were 76.6% and 68.9%. Local tumor control and secondary resection rate (Arm A: 4%; Arm B: 16%) were significantly improved in Arm B. Median PFS was 6.8 months with distant metastasis as main treatment failure. ConclusionTrimodal therapy consisting of IMRT, gemcitabine and cetuximab can be considered safe and feasible. Compared to historical data, cetuximab does not improve treatment efficacy in LAPC patients treated with chemoradiation.

Gemcitabine Maintenance Therapy in Patients With Metastasized Soft Tissue Sarcomas.

BackgroundMetastasized soft-tissue sarcomas still pose a significant therapeutic challenge given the limited efficacy of currently available multimodal treatment strategies. Recent progress in molecular characterization of sarcoma subtypes has enabled successful personalized therapy approaches in a minority of selected patients with targetable mutations. However, in the majority of patients with refractory soft tissue sarcomas, long-term survival remains poor.MethodsWe report on three adult patients with various soft tissue sarcomas subjected to Gemcitabine maintenance therapy. Tumor entities included leiomyosarcoma of the pancreas (patient 1), undifferentiated pleomorphic sarcoma of the right femur (patient 2), and peri-aortic leiomyosarcoma (patient 3). Metastatic sites encompassed liver, lung, and bones. All patients received Gemcitabine maintenance therapy until disease progression following prior salvage chemotherapy with Docetaxel and Gemcitabine. Patients were treated outside of clinical trials. Response assessment was based on radiological imaging.ResultsIn response to salvage chemotherapy with Docetaxel and Gemcitabine, one patient exhibited a partial remission, and two patients showed stable disease. Patient 1 exhibited stable disease for 6 months during Gemcitabine maintenance therapy before suffering rapid progression of hepatic metastases. Patient 2 underwent 21 months of Gemcitabine maintenance therapy, which was discontinued after progressive pulmonary metastases were detected. Patient 3 is still being treated with Gemcitabine maintenance therapy. Remarkably, owing to significant chemotherapy-associated hematotoxicity, the dose of Gemcitabine dose was reduced by two-thirds. Nevertheless, stable disease with constant pulmonary metastases has been maintained in this patient for 14 months.ConclusionsGemcitabine maintenance therapy following prior Docetaxel and Gemcitabine chemotherapy is manageable and reveals potential benefits for patients with aggressive metastasized soft tissue sarcomas. Prospective trials evaluating Gemcitabine maintenance therapy are encouraged.

Immune monitoring in mesothelioma patients identifies novel immune-modulatory functions of gemcitabine associating with clinical response.

BackgroundGemcitabine is a frequently used chemotherapeutic agent but its effects on the immune system are incompletely understood. Recently, the randomized NVALT19-trial revealed that maintenance gemcitabine after first-line chemotherapy significantly prolonged progression-free survival (PFS) compared to best supportive care (BSC) in malignant mesothelioma. Whether these effects are paralleled by changes in circulating immune cell subsets is currently unknown. These analyses could offer improved mechanistic insights into the effects of gemcitabine on the host and guide development of effective combination therapies in mesothelioma.MethodsWe stained peripheral blood mononuclear cells (PBMCs) and myeloid-derived suppressor cells (MDSCs) at baseline and 3 weeks following start of gemcitabine or BSC treatment in a subgroup of mesothelioma patients included in the NVALT19-trial. In total, 24 paired samples including both MDSCs and PBMCs were included. We performed multicolour flow-cytometry to assess co-inhibitory and-stimulatory receptor- and cytokine expression and matched these parameters with PFS and OS.FindingsGemcitabine treatment was significantly associated with an increased NK-cell- and decreased T-regulatory cell proliferation whereas the opposite occurred in control patients. Furthermore, myeloid-derived suppressor cells (MDSCs) frequencies were lower in gemcitabine-treated patients and this correlated with increased T-cell proliferation following treatment. Whereas gemcitabine variably altered co-inhibitory receptor expression, co-stimulatory molecules including ICOS, CD28 and HLA-DR were uniformly increased across CD4+ T-helper, CD8+ T- and NK-cells. Although preliminary in nature, the increase in NK-cell proliferation and PD-1 expression in T cells following gemcitabine treatment was associated with improved PFS and OS.InterpretationGemcitabine treatment was associated with widespread effects on circulating immune cells of mesothelioma patients with responding patients displaying increased NK-cell and PD-1 + T-cell proliferation. These exploratory data provide a platform for future on treatment-biomarker development and novel combination treatment strategies.

Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer

PurposeDespite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.Materials and MethodsPatients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.ResultsSeventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.ConclusionAdjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Real world experience on maintenance chemotherapy with gemcitabine in second line setting for advanced non-small cell lung carcinoma

Maintenance chemotherapy was studied in first line setting for advanced stage non-small cell lung carcinoma (NSCLC). There has not been any data on the role of continuation maintenance chemotherapy in second line setting. A retrospective cohort study that included 226 patients with advanced stage NSCLC that received second line gemcitabine ± platinum was conducted. Patients who had continuation maintenance gemcitabine were compared with those who went on drug holiday. The primary endpoint was progression-free survival (PFS), counted from the end of induction therapy. The median PFS was significantly longer for patients who continued with maintenance gemcitabine when compared with those on drug holiday (5.6 vs 1.7 months, HR 0.392, p-value < 0.001). The overall survival was also significantly longer (21.4 vs 15.8 months, HR 0.508, p-value 0.047). There was no increase in incidence of adverse events for patients who underwent maintenance gemcitabine. Continuation maintenance therapy with gemcitabine in second line setting is a potentially feasible and safe option for patients with advanced NSCLC.

Gemcitabine maintenance versus observation after first-line chemotherapy in patients with metastatic urothelial carcinoma: a retrospective study.

BackgroundGemcitabine with platinum is one of the most important first-line treatments for metastatic urothelial cancer (mUC). However, continuation of platinum agents results in cumulative toxicities, such as nephrotoxicity, ototoxicity, and neurotoxicity, which lead to discontinuation of chemotherapy after 4–6 cycles despite a favorable response in the patients. The strategy of maintenance treatment can give clinical benefit to patients, but there is no consensus about maintenance treatment. The aim of this study was to investigate the clinical impact of the gemcitabine maintenance (GEM-m) in mUC patients who achieve disease control from first-line gemcitabine with platinum agents.MethodsA total of 117 patients who showed response to 4–6 cycles of gemcitabine plus cisplatin or carboplatin as the first-line palliative chemotherapy were reviewed between 2014 to 2018. Patients who were treated with GEM-m received a 1,000 mg/m2 dose of gemcitabine on day 1 and 8 for 3 weeks until disease progression or development of unacceptable toxicity. The patients who are not treated with GEM-m were followed up with regular radiologic evaluation. Statistical analyses were performed using the log-rank test and Cox proportional hazards method.ResultsFifty-eight patients (49.6%) received GEM-m. The median cycle of GEM-m was 4 (range, 1–12). Six patients (10.3%) in the GEM-m group showed an objective response. A median overall survival (OS) of 11.8 months and 9.6 months was observed for the GEM-m and non-GEM-m groups, respectively [HR 0.621; 95% CI, 0.39–0.97; P=0.026]. Additionally, median progression-free survival (PFS) was 4.6 months and 3.3 months in the GEM-m and non-GEM-m groups, respectively [HR 0.612; 95% CI, 0.41–0.91; P=0.009]. Grade 3 or higher neutropenia occurred in 17.2% of patients in the GEM-m and 1.7% in the non-GEM-m group.ConclusionsOur results suggest that GEM-m can be considered in patients who respond to gemcitabine with platinum. Large-scale prospective study should be warranted.

Role of Maintenance Gemcitabine in Advanced Carcinoma Gallbladder.

Objective The aim of this study is to investigate the effects of gemcitabine maintenance on progression-free survival (PFS) in patients with metastatic gallbladder cancer (GBC). Materials and Methods Sixty patients with unresectable or metastatic GBC having ongoing response to treatment with initial six cycles of gemcitabine and a platinum-based doublet chemotherapy were prospectively randomized on day 21 of the 6th cycle in 1:1 fashion to receive either maintenance gemcitabine 1 g/m 2 intravenously on day 1 and day 8 of three weekly cycle or observation. Survival analysis was performed using the Kaplan–Meier method and comparisons by the log-rank test. A p -value < 0.05 was considered as statistically significant. Results Of 60 patients, a total of 56 were available for final analysis. The median PFS was 4.7 months (3.1–6.3) in gemcitabine arm and 2.6 months (2.4–2.8) in observation arm, hazard ratio (HR) 0.196 (95% confidence interval [CI]: 0.1–0.39), p < 0.001. Median overall survival in gemcitabine arm was 12.4 months (9.15–15.6) as opposed to 9.9 months (8.29–11.5) in observation arm, HR 0.76 (95% CI: 0.43–1.35), p = 0.354. The grade 3 or 4 side effects in maintenance arm were transaminitis (17.9%), thrombocytopenia (17.8%), neutropenia (14.2%), and febrile neutropenia (7.1%). Conclusions Maintenance gemcitabine therapy in unresectable/metastatic GBC patients responding to first-line gemcitabine and platinum treatment contributes to increase PFS with minimal and manageable side effects.

Switch Maintenance Gemcitabine after First Line Chemotherapy in Patients with Malignant Mesothelioma: A Randomized Open Label Phase II Trial (NVALT19)

Background: All patients with malignant mesothelioma develop progressive disease after first line therapy. Some studies have addressed maintenance therapy, none showed a great impact. Gemcitabine, an active drug in mesothelioma, was tested in the NVALT19 study in a switch maintenance setting. Methods: This open label randomized phase II study in 18 Dutch hospitals, recruited patients with unresectable mesothelioma who did not progress after first line chemotherapy (platinum-pemetrexed), World Health Organization performance status ≤ 2 and an adequate organ function. Key exclusion criteria were seriously disabling conditions or symptomatic central nervous system metastases. Patient were 1:1 randomised to maintenance gemcitabine (1250 mg/m2, intravenous, day 1 and 8, 3 weeks schema) or best supportive care (BSC,) using minimisation method. Primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Safety was analysed in all participants who received one dose of study drug. Findings: From March 20, 2014, to February 27, 2019, 130 patient were randomized (65 to gemcitabine and 65 to BSC). PFS was significant longer with gemcitabine (median 6.2) than with BSC (3·2 months; hazard ratio (HR) 0·46; 95% confidence interval [CI], 0·31 to 0·68; p<0·001). The benefit was confirmed by independent central review (HR 0·47; 95% CI, 0·32 to 0·69; p<0·001). Grade 3- 4 adverse events occurred in 33 (51%) patients in the gemcitabine arm and in 10 (16%) patients in the BSC arm. One patient died likely due to a gemcitabine related infection. Interpretation: Switch maintenance gemcitabine, after first line chemotherapy, significantly prolonged progression free survival compared to BSC alone among patients with malignant mesothelioma. The study confirmed the activity of gemcitabine in malignant mesothelioma. Trial Registration: This study is registered in the Netherlands Trial registry; NTR4132/NL3847. Funding Statement: Dutch Cancer Society (KWF Kankerbestrijding) and the NVALT Study Group. Declaration of Interests: PB participated in advisory boards of Merck Sharp & Dohme and Bristol-Myers Squibb. RC participated in advisory boards of Merck Sharp & Dohme and Roche, and received speakers fee from Roche, Pfizer and BristolMyers Squibb. HJMG has received research funding from Lilly, Novartis, Roche-Genentech, and Takeda (all to institution). JGA reports personal fees and non-financial support from msd, personal fees from bms, personal fees from boehringer ingelheim, personal fees from amphera, personal fees from eli-lilly, personal fees from takeda, personal fees from bayer, personal fees from roche, personal fees from astra zeneca, outside the submitted work; In addition, JGA has a patent allogenic tumor cell lysate licensed to amphera, a patent combination immunotherapy in cancer pending, and a patent biomarker for immunotherapy pending. JAB reports reimbursement from Bristol-Myers Squibb and F Hoffmann-La Roche for the Netherlands Cancer Institute, and financial support for an investigator initiated trial from Merck Sharp & Dohme. CJG, VvdN, JAS, BB, NvW, RvH, MYES, AJS, WAB, GPB, FD, HvT, FL declare no competing interests. Ethics Approval Statement: The research protocol has been approved by the central ethical committee and local institutional review boards. All patients provided written informed consent.

LBA92 - Switch maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma: A multicenter open label phase II trial (NVALT19)

BackgroundAll malignant mesothelioma (MM) patients progress after first-line therapy. We examined whether switch maintenance gemcitabine in patients, who did not show progression after first-line platinum-pemetrexed, could prolong time to disease progression. MethodsNVALT19 was an open label, randomized phase II trial, conducted in The Netherlands. Main eligibility criteria were pathologically proven MM, ECOG-PS 0-2 and completion of 4-6 cycles of first-line platinum-pemetrexed without progression. Patients were randomized 1:1 between gemcitabine (1250mg/m2day 1 and 8 of 3 weekly schedule) or best supportive care (BSC). Gemcitabine was given until disease progression, severe toxicity or patient request for discontinuation. Primary endpoint was progression free survival (PFS) determined by local physician according to modified RECIST (mRECIST) or death in the intention-to-treat population. It was computed that 118 events would yield 90% power to detect an increase in PFS from median 3.5 months to median 6 months at 90% confidence level. ResultsBetween March 2014 and February 2019, 130 patients were randomized, 65 in each arm. PFS was significantly longer with gemcitabine (median 6.2 months [range 4.6-8.7m]) than in the BSC arm (3.2 [2.8-4.2m]; hazard ratio 0.42; 95% confidence interval [CI], 0.28-0.63; p<0.0001). The PFS probability at 12 months was 25% for Maintenance Gemcitabine (95% CI: 16.3 - 38.5%) and 3.3% for BSC (95% CI: 0.8 - 13%). Central revision of PFS, by a blinded radiologist, also showed significant benefit for gemcitabine (median 5.3 months [4.2-7.1m]) above BSC (2.8 [2.5-3.3m]; hazard ratio 0.42; 95% CI 0.28 to 0.62; p<0.0001). Grade 3-4 adverse events (AE) occurred more in the gemcitabine arm (57% of patients) vs 13% in the BSC-arm. Neutropenia (22%), nausea (6%) and lung infection (5%) were most common treatment related grade III AE’s. Three patients (5%) experienced grade IV neutropenia. One patient died in the gemcitabine arm due to treatment related sepsis. Data on dose intensity will follow at ESMO 2019. ConclusionsSwitch maintenance gemcitabine after first-line chemotherapy significantly improves the PFS in malignant mesothelioma, with a manageable toxicity profile. Clinical trial identificationNTR4132. Legal entity responsible for the studyStichting NVALT studies. FundingDutch Cancer Society and Stichting NVALT studies. DisclosureAll authors have declared no conflicts of interest.

A Phase II Study of Cisplatin Plus Gemcitabine followed by Maintenance Gemcitabine for Advanced Squamous Non-Small-Cell Lung Cancer: Kyoto Thoracic Oncology Research Group 1302

Background: There has been no study so far on gemcitabine continuous maintenance therapy targeting only squamous non-small-cell lung cancer (NSCLC) patients. This study aimed to assess the efficacy and safety of cisplatin plus gemcitabine followed by maintenance gemcitabine for chemotherapy- naïve Japanese patients with advanced squamous NSCLC. Methods: The patients received 4 cycles of gemcitabine (1,000 mg/m², days 1 and 8) and cisplatin (80 mg/m², day 1) every 3 weeks, followed by gemcitabine alone as maintenance therapy every 3 weeks until disease progression or unacceptable toxicity. The primary end point of the study was progression-free survival (PFS) from the date of registration. Results: From May 2013 to October 2018, 26 patients were enrolled, and 25 patients received ≥1 cycle of planned treatment. Eighteen patients (69.2%) received 4 cycles of cisplatin plus gemcitabine, and 16 patients (61.5%) received ≥1 cycle of maintenance gemcitabine. The median PFS from the date of registration was 5.3 months (95% CI 2.9–7.3 months). In 16 patients who received ≥1 cycle of maintenance gemcitabine, the median PFS from the date of maintenance gemcitabine initiation was 3.8 months (95% CI 2.3–5.2 months). Their median overall survival from the date of registration was 11.9 months (95% CI 7.5–26.5 months). During the maintenance therapy, adverse events (AEs) were mostly Common Terminology Criteria for AE grade 1. Conclusions: While this trial did not meet the primary endpoint, the sufficient efficacy and feasibility of gemcitabine maintenance therapy were suggested.

P-063 - Role of maintenance gemcitabine in advanced and metastatic carcinoma gall bladder

P-063 - Role of maintenance gemcitabine in advanced and metastatic carcinoma gall bladder

Successful treatment with GEMOX in patient with metastatic pancreatic adenosquamous carcinoma.

Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer characterized by a dual histological component and aggressive behavior. This form is not well known, its histogenesis is uncertain, and there are different opinions on the diagnostic histopathological criteria. The differential diagnosis with more common ductal adenocarcinoma, squamous cell carcinoma, squamous or adenosquamous metastases is complex. The available therapies do not improve the poor prognosis and it is difficult to find long-term survivors (more than 1 year), even after demolitive surgery with complementary therapies. We report a case of advanced PASC with excellent progression-free survival and overall survival, 20 months and 29 months, respectively. Furthermore, an almost complete response was obtained to first-line chemotherapy with gemcitabine/oxaliplatin (GEMOX) followed by maintenance gemcitabine. GEMOX followed by gemcitabine as maintenance could be an effective treatment for this pancreatic entity. Further reports are needed to confirm this outcome.

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival.

To investigate the effects of gemcitabine maintenance treatment on survival in patients with metastatic bladder cancer. Gemcitabine maintenance monotherapy was administered following the standard platinum-gemcitabine therapy in patients with metastatic bladder cancer. Patients who had responded to standard treatment received maintenance gemcitabine therapy as 1000 mg/m2 on days 1 and 8 every three weeks until progression or development of unacceptable toxicity. The following clinical factors were noted: performance status, age, sex, stage, site of metastasis, choice of cisplatin-gemcitabine or carboplatin-gemcitabine, response rates to the initial chemotherapy. Progression-free survival (PFS) and overall survival (OS) for standard treatment, and following gemcitabine monotreatment and for maintenance gemcitabine therapy were calculated using Kaplan-Meier method. A total of 88 patients with metastatic bladder cancer treated between February 2009 to October 2015 were evaluated retrospectively and 23 patients (26.1%) who had responded to six cycles of platinum-gemcitabine treatment were included in this study. Maintenance gamcitabine was administered for a median of 7 times (range 3-14 times). Grade 3 hematotoxicity according to the criteria of the Common Terminology Criteria of Adverse Events was observed in 7 (30.4%) patients. Median PFS of patients was 46 (range: 30-82) weeks for platinum-based treatment plus maintenance gemcitabine therapy. A higher median PFS was obtained in patients who were <65 year-olds, without organ metastasis with objective response rate, however, it was statistically insignificant. Gemcitabine maintenance therapy in metastatic bladder cancer patients who did not shown progression after the standard platinum-gemcitabine treatment contributes to survival and presents low toxicity profile, when compared to historical controls.

Does "OPTINAB" strategy ("stop-and-go") work in treatment of advanced pancreatic cancer (APC) with nab-paclitaxel-gemcitabine?

MPACT demonstrated a survival benefit of nab-paclitaxel plus gemcitabine versus gemcitabine in advanced pancreatic cancer (APC). However, sensory peripheral neuropathy is a dose-limiting toxicity and neuromodulators have shown limited, if any activity in ameliorating neuropathy. In colorectal cancer, the OPTIMOX ("stop-and-go") approach offered a strategy to reduce neuropathy. No data exist to support this strategy for nab-paclitaxel in APC. Retrospective study of APC patients who developed grade 3 neuropathy during nab-paclitaxel plus gemcitabine was done. Nab-paclitaxel was held and then reinstituted upon radiological or tumor marker progression. Duration of disease control (DCC) was measured. We named this strategy "OPTINAB". Seven patients out of 27 (25%) developed grade 3 neuropathy after an average of 4.2months; nab-paclitaxel was suspended while gemcitabine was continued. Maintenance gemcitabine continued for a mean of 2.8months. Upon progression (radiologic or CA19-9) nab-paclitaxel was re-instituted with gemcitabine. One patient could not tolerate nab-paclitaxel due to worsening of neuropathy while other six continued the combo with mean progression-free survival 2 (PFS2) of 2.2months. The six patients continued nab-paclitaxel for a mean of PFS2 of 2.2months (range 1-4months). Nab-paclitaxel resulted in improvement of an average DDC with an average of (7.0+2.2=) 8.2months (range 8-13months). Average overall survival for this group was 11.7months (range 9.5-17months). Reintroduction of nab-paclitaxel resulted in an average DDC of 9.4months. Average overall survival (OS) for this group was 11.7months. "OPTINAB" approach improved PFS2 in these patients and was feasible as majority of the patient tolerated nab-paclitaxel. Although it is a small study, it supports the need for a randomized, prospective study to test the concept of "OPTINAB".

Maintenance gemcitabine versus best supportive care following platinum-paclitaxel chemotherapy for patients with advanced nonsmall cell lung cancer

Background: Approximately two-thirds of all patients with newly diagnosed nonsmall cell lung cancer (NSCLC) have advanced disease (Stage IIIB or IV) that is only amenable to palliative chemotherapy. Switch maintenance therapy with a different active agent aims to hit clonal variants resistant to the first-line therapy before they have had time to increase in number. Based on this, we conducted a randomized Phase III study to compare gemcitabine (Gem) versus best supportive care (BSC) as maintenance therapy. Methods: Between July 2011 and January 2012, chemo-naive patients with Stage IIIB/IV NSCLC were initially treated with six cycles of cisplatin (40 mg/m2 day 1, 2) and paclitaxel (175 mg/m2 day 1) every 3 weeks. Subsequently, nonprogressors were randomized 1:1 to receive maintenance G (1000 mg/m2 on days 1 and 8 every 3 weeks) or BSC alone till disease progression. The primary endpoint was a comparison of overall survival (OS) between two arms, and the secondary endpoint was progression-free survival (PFS). Results: Exactly 134 patients were enrolled (median age: 50 years, males 76.8%, Stage IV disease 50.7%, Eastern Cooperative Oncology Group performance status 0/1: 67.9%). Following 6 cycles of initial therapy, the Response Rate (RR) was 35.1% (Complete Response (CR) 3%, Partial Response (PR) 32.1%), and 38.8% had stable disease. Ninety-nine nonprogressors were randomized to receive Gem (n = 50) or BSC (n = 49). The median OS for Gem was 10 months (95% confidence interval [CI]: 9.2–10.7) and 8 months (95% CI: 6.7–9.2) for BSC, with a hazard ratio (HR) 0.64 (95% CI: 0.51–0.77, P = 0.002). The median PFS was 9 months (95% CI: 8.1–9.9) for G versus 7 months (95% CI: 6.3–7.7) for BSC, with a HR 0.67 (95% CI: 0.50–0.84, P = 0.009). Maintenance therapy was tolerated well despite a higher incidence of grade 3/4 toxicity (anemia 12% vs. 8.1%; neutropenia 18% vs. 4.1%; thrombocytopenia 14% vs. 2%; and fatigue 8% vs. 2%). Conclusion: Switch maintenance therapy with gemcitabine, following initial platinum-based doublet chemotherapy in advanced NSCLC can produce significantly longer PFS and OS compared to BSC alone at the cost of higher grade 3/4 hematological toxicities.

100PD - A Prospective Randomized Open Label Phase III Study of Maintenance Gemcitabine Versus Best Supportive Care Following Platinum-Paclitaxel Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer

Aim: Approximately two-thirds of all patients with newly diagnosed non-small-cell lung cancer (NSCLC) have advanced disease (stage IIIB or IV) that is only amenable to palliative chemotherapy. Switch maintenance therapy with a different active agent aims to hit clonal variants resistant to the first-line therapy before they have had time to increase in number. Based on this, we conducted a randomized phase III study to compare Gemcitabine (G) versus Best Supportive Care (BSC) as maintenance therapy for patients with advanced NSCLC. Methods: Between July 2011 and January 2012, chemo-naive patients with stage IIIB/IV NSCLC were initially treated with six cycles of cisplatin (40 mg/m2 day 1, 2) and paclitaxel (175 mg/m2 day 1) every 3 weeks. Subsequently, non-progressors were randomized 1:1 to receive maintenance G (1000 mg/m2 on days 1 and 8 every 3 weeks) or BSC alone till disease progression. The primary endpoint was the comparison of overall survival (OS) between the two arms and the secondary endpoint was progression free survival (PFS). The survival analyses were performed by using SPSS version 20.0. Results: 134 patients were enrolled (median age: 50 years, males 76.8%, stage IV disease 50.7%, ECOG performance status 0/1: 67.9%). Following 6 cycles of initial therapy, the RR was 35.1% (CR-3%, PR-32.1%), and 38.8% had SD. 99 non-progressors were randomized to receive G (n = 50) or BSC (n = 49). The median OS for G was 10 months (95% CI: 9.2-10.7) and 8 months (95% CI: 6.7-9.2) for BSC, with a hazard ratio (HR) 0.64 (95% CI: 0.51-0.77, P = 0.002). The median PFS was 9 months (95% CI: 8.1-9.9) for G versus 7 months (95% CI: 6.3-7.7) for BSC, with a HR 0.67 (95% CI: 0.50-0.84, P = 0.009). Maintenance therapy was tolerated well despite a higher incidence of grade 3/4 toxicity (anemia 12% vs. 8.1%; neutropenia 18% vs. 4.1%; thrombocytopenia 14% vs. 2%; and fatigue 8% vs. 2%). Conclusions: Switch maintenance therapy with gemcitabine, following initial platinum-based doublet chemotherapy in advanced NSCLC can produce significantly longer PFS and OS compared to BSC alone at the cost of higher grade 3/4 hematological toxicities. Disclosure: All authors have declared no conflicts of interest.

Maintenance monotherapy with gemcitabine after standard platinum-based chemotherapy in patients with advanced urothelial cancer.

To investigate the outcomes of gemcitabine maintenance monotherapy treatment for metastatic urothelial cancer. Gemcitabine maintenance monotherapy was used for metastatic urothelial cancer patients after standard platinum-based chemotherapy. A standard dose of 1000 mg/m(2)/month was given. If patients suffered adverse events or a noticeably compromised quality of life, treatment intervals were extended and doses lowered. Patients with metastatic urothelial cancer receiving only best supportive care after standard chemotherapy served as the retrospective control group. A total of 33 patients were included in the study group as well as in the control group. Maintenance therapy was administered a median of nine times (range 2-49 times) with a median dose of 984.2 mg (range 500-1400 mg) per time. An adverse event of the Common Terminology Criteria of Adverse Events grade 3 or greater was observed in 10 (30.3%) patients, while nine patients (27.3%) experienced hematotoxicity. After standard chemotherapy pretreatment, disease-specific survival in the maintenance therapy group was an average of 15.0 months, significantly more favorable (P < 0.001) than that of the control group (4.0 months). On multivariate analysis, efficacy of prior chemotherapy (P = 0.018), visceral metastasis (P = 0.007) and gemcitabine maintenance therapy (P < 0.001) were statistically significant prognostic parameters of disease-specific survival. The present study findings suggest that gemcitabine maintenance monotherapy in metastatic urothelial cancer might not only be useful as a palliative treatment, but it could also have a certain level of therapeutic effectiveness.