Activity Of Single-agent Gemcitabine Research Articles

Activity of single-agent gemcitabine in patients (pts) with advanced angiosarcoma: A retrospective study.

e23547 Background: Gemcitabine has shown clinical activity against angiosarcoma in single cases or small series, as a single agent or in combination with taxanes. We aimed to evaluate its activity in a larger, homogeneous series of pts with advanced angiosarcoma. Methods: We retrospectively reviewed the electronic medical records of consecutive adult pts with advanced angiosarcoma treated with gemcitabine(1000 mg/m2 IV days 1, 8 and 15 of a 28-days cycle) at our institutions from January 2010 to January 2021. All cases were confirmed by an expert pathologist from the French network of Sarcoma pathologists (RRePS). Response was evaluated according to RECIST 1.1, and survival was estimated using the Kaplan-Meier method. Results: Fourty-two pts [median age : 52 years (range : 25-90), median PS : 1 (range : 0-2), 36 women)] were identified. Ten (24%) had locally advanced disease; the median number of metastatic sites was 2 (range : 1-4) in the remaining 32 pts. Primary tumor site was breast/chest wall (12), face/scalp (9), heart (8), other viscera (7) or limbs (7). Eleven (26%) occurred in previously irradiated field. All pts but 4 had received prior anthracyclines (peri-operatively or in the metastatic setting) and weekly paclitaxel, and 9 (21%) had received pazopanib. Gemcitabine was given as second, third and fourth line in 7 (17%), 20 (47%) and 15 (36%) pts, respectively. Best tumor response by RECIST 1.1 was PR (16 pts, 38%), SD (10 pts, 24%) or PD (16 pts, 38%). All pts with cardiac angiosarcoma experienced a PR, as well as 4 of 10 pts with angiosarcoma arising in irradiated field and 3 of the 4 pts with CNS metastases. Median PFS was 5.4 months (95%CI : 3.1-6.5), and median OS was 9.9 months (95%CI : 6.6-13.4). Two febrile neutropenia occurred. No new safety signal was observed. Ongoing studies are exploring whether candidate biomarkers such as hENT1 expression could help predicting the benefit of gemcitabine in pts with angiosarcoma of the heart and large vessels. Conclusions: Single agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma (including cardiac angiosarcoma). This series may serve as a benchmark for future clinical trials in angiosarcoma.

Gemcitabine in patients previously treated with platinum-containing chemotherapy for refractory thymic carcinoma: radiographic assessment using the RECIST criteria and the ITMIG recommendations

The key drugs for chemotherapy of thymic carcinoma are gradually being revealed in phase II and conventional retrospective studies. Gemcitabine is regarded as one of these key drugs according to the findings of clinical trials in which it was combined with capecitabine. However, the activity of single-agent gemcitabine concerning refractory thymic carcinoma remains unclear. We conducted a retrospective review of the medical records of refractory thymic carcinoma patients previously treated with platinum-containing chemotherapy between 1980 and 2014. Of all 11 patients in this study, the objective response rate regarding gemcitabine was 36.4% [95% confidence interval (CI) 15.2-64.6] using the RECIST criteria and the response criteria proposed by the ITMIG. The median progression-free survival time was 4.3months (95% CI 0.7-11.0). The survival time from the start of gemcitabine treatment was 28.5months (95% CI 5.5-47.8), and from the start of first-line chemotherapy was 46.5months (95% CI 7.3-47.8). Gemcitabine achieved a moderate response and has the potential to be used as a key drug for thymic carcinoma. Some patients treated with gemcitabine demonstrated prolonged cancer control even in later lines of chemotherapy.

Clinical activity of single-agent gemcitabine in a single-center series of 83 malignant pleural mesothelioma after failure of pemetrexed-based chemotherapy.

e18547 Background: No standard second line chemotherapy (CT) has been yet established for Malignant Plural Mesothelioma (MPM) after failure of pemetrexed based CT. Aim of this study was to evaluate...

The Use Of GDP (Gemcitabine, Dexamethasone and Cisplatin) in The Primary Therapy Of Peripheral T-Cell Lymphomas

IntroductionThe outcome of peripheral T-cell lymphomas (PTCLs) is poor using standard CHOP chemotherapy. Previous studies have shown good single agent activity of gemcitabine in the relapsed/refractory setting. GDP (gemcitabine, dexamethasone and cisplatin) was developed as a secondary chemotherapy regimen in relapsed aggressive lymphomas and in a comparison to DHAP has recently been shown to have equivalent efficacy, a favourable side effect profile, and it can be delivered in the outpatient setting. At the BC Cancer Agency, GDP has recently been integrated into the primary therapy of patients with PTCLs in an attempt to improve outcomes with CHOP chemotherapy in this poor risk population. MethodsThe BC Cancer Agency Centre for Lymphoid Cancer and pharmacy databases were searched to identify all cases of newly diagnosed PTCLs with diagnoses by the WHO classification, (with the exception of ALK-positive ALCL, extranodal NK/T-cell lymphoma, cutaneous T-cell lymphoma and hepatosplenic t-cell lymphoma) that received at least one cycle of GDP chemotherapy integrated into their primary therapy, typically alternating with CHOP. ResultsIn total, 34 patients received GDP as part of their first-line treatment (PTCL-NOS n=19, ALK-neg ALCL n=10, enteropathy-type TCL n=2, angioimmunoblastic T-cell lymphoma n=3) in addition to CHOP chemotherapy. The median age was 58 years, 65% were male and the majority of patients had high risk features including stage 3 or 4 disease (94%), elevated LDH (62%). high IPI score (>3 65%; >2 82%) and 32% had bone marrow involvement. The median number of cycles of GDP was 3 (1-8). Two patients underwent consolidative treatment with high dose chemotherapy and autologous stem cell transplantation in first remission and two patients received consolidative radiotherapy. The overall response rate at the end of primary chemotherapy was 82% (CR 62%). With a median follow-up in living patients of 2.8 years the 1- and 2-year time to progression (TTP) were 50% and 36%, respectively and the corresponding estimates for OS were 78% and 64%. Interestingly, the IPI was not prognostic (2 y TTP IPI 0,1 42%, 2,3 34%%, 4,5 37.5% p=.87) even if the 2 patients undergoing transplant are excluded. GDP was generally well tolerated and only 2 patients discontinued treatment due to toxicity (renal dysfunction/hearing loss and rash) and there were no treatment-related deaths. Two patients were hospitalized for febrile neutropenia following GDP and 9 patients (26%) required GCSF support through their therapy. ConclusionThe use of GDP in the primary treatment of PTCL is associated with a high response rate. Outcomes in high IPI patients compare favourably with historical results using CHOP chemotherapy and suggest that it may be able to overcome disease resistance in this poor risk group, providing rationale to explore it in further in future clinical trials of PTCLs. Disclosures:Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Savage:Eli-Lilly: Consultancy.

Single agent gemcitabine in the second-line treatment of advanced non-small cell lung cancer after treatment with taxane + platinum regimens

In this study, we investigated the activity of single agent gemcitabine in the second-line setting of non-small cell lung cancer (NSCLC). File records of 21 patients treated with single agent gemcitabine in advanced NSCLC who received one prior chemotherapy including a taxane and platinum combination were retrospectively evaluated. Treatment consisted of IV gemcitabine 1,250 mg/m2 on days 1 and 8, followed by a 1-week rest repeated every 3 weeks. A partial response was achieved in four (19%) patients. The median response duration was 16 (range, 12-32) weeks. Six (29%) patients had a SD more than 3 months. The median time to progression was 16 (range, 8-32) weeks. No complete response was observed. Median overall survival was 36 weeks for second-line gemcitabine in all patients (95%: CI 5-13 months). Hematological toxicity (all grades) was reported by 9 (42.9%) patients. One (4.75%) patient experienced grade 3/4 neutropenia. Grade 3/4 nausea and vomiting and mucositis were reported in one (4.75%) patient. In conclusion, this study shows that single agent gemcitabine is active and well tolerated as a second-line therapy for advanced NSCLC.

N0234: Phase II study of erlotinib (OSI-774) plus gemcitabine as first-or second-line therapy for metastatic breast cancer (MBC)

644 Background: Based on favorable preclinical interaction of the HER1 inhibitor erlotinib with chemotherapy, and previously demonstrated single agent activity of gemcitabine as therapy for metastatic breast cancer (MBC), a phase II study of the combination was conducted by the North Central Cancer Treatment Group. Goals were to evaluate the anti-tumor activity and tolerability of erlotinib 150 mg P.O. daily in combination with gemcitabine at 1000 mg/m2 days 1 and 8 of 21 day cycles. Eligibility: MBC, measurable disease as defined by RECIST. Prior adjuvant chemotherapy and up to 1 prior chemotherapy for MBC allowed (1 of which had to include an anthracycline or taxane). Results: 59 evaluable patients were enrolled. Patient characteristics: median age: 57 (range: 28–82), prior adjuvant chemotherapy (68%), prior anthracycline (81%), prior taxane (78%), prior anthracycline and taxane (61%); 0 prior chemotherapy for MBC (44%), 1 prior chemotherapy for MBC (56%). Median number of cycles treatment administered: 4 (range: 1–17). Severe (CTC grade 3/4) hematologic adverse events: neutropenia (35%), thrombocytopenia (9%), and anemia (7%). Severe (CTC grade 3/4) non-hematologic adverse events: fatigue (14%), dyspnea (12%), diarrhea (9%), rash (7%), and infection (4%). 10 pts are still receiving study treatment (tx). Reasons for discontinuing tx: disease progression (76%), patient refusal (12%), adverse event (4%), new primary (2%), symptomatic deterioration (4%), and patient no return (2%). Response: 8 partial responses for an overall response rate of 14% (95% CI: 6–25%). Median duration of response was 4.6 months. At last contact, 12 pts were alive without progression and 28 alive with progression (median length of follow-up 4.3 months; max follow-up of 12 months), and 19 died. Median PFS was 2.8 months (95%CI: 1.9–4.2 months). The 6-month survival rate was 75% (95%CI: 63–89%). Conclusions: The combination of Erlotinib plus gemcitabine was well tolerated. This combination has lower than expected activity as 1st or 2nd-line therapy for MBC, based on historical controls of gemcitabine based combination treatment. Partial support by Breast Cancer Research Foundation and NIH (CA25224). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer

Chemotherapy for biliary tract cancer in Japan

The incidence of biliary tract cancer has increased markedly in Japan over the past several decades and ranks as the sixth leading cause of cancer death. Currently, there is no standard chemotherapy for biliary tract cancer. Early phase investigation of cisplatin and cisplatin/epirubicin/5-fluorouracil yielded disappointing results in this setting. Gemcitabine is currently approved for use in the treatment of non–small cell lung cancer and pancreatic cancer in Japan. Based on the single-agent activity of gemcitabine in biliary tract cancer in other locales combined with the drug's established safety profile, gemcitabine is currently being evaluated as single-agent therapy in the treatment of advanced biliary tract cancer patients in Japan. Semin Oncol 29 (suppl 20):51-53. Copyright 2002, Elsevier Science (USA). All rights reserved.

Chemotherapy for biliary tract cancer in Japan.

The incidence of biliary tract cancer has increased markedly in Japan over the past several decades and ranks as the sixth leading cause of cancer death. Currently, there is no standard chemotherapy for biliary tract cancer. Early phase investigation of cisplatin and cisplatin/epirubicin/5-fluorouracil yielded disappointing results in this setting. Gemcitabine is currently approved for use in the treatment of non-small cell lung cancer and pancreatic cancer in Japan. Based on the single-agent activity of gemcitabine in biliary tract cancer in other locales combined with the drug's established safety profile, gemcitabine is currently being evaluated as single-agent therapy in the treatment of advanced biliary tract cancer patients in Japan.

Activity of single-agent gemcitabine as second-line treatment after previous chemotherapy or radiotherapy in advanced non-small-cell lung cancer

The aim of the study was to evaluate activity, toxicity and health-related quality of life (HRQL) with gemcitabine as second-line treatment after previous chemo- or radiotherapy in non-small-cell lung cancer (NSCLC). Patients with previously treated NSCLC were treated with gemcitabine (1000 mg/m 2) on days 1, 8 and 15 in a 28-day cycle. Eighty patients were included; median age was 57 years (range 38–77). Prior treatment consisted of platinum-containing chemotherapy in 29 patients and high-dose thoracic radiotherapy in 51 patients. Median number of cycles was three (range 1–6). Granulocytopenia CTC grade 3 and 4 occurred in 9% and thrombocytopenia CTC grade 3 and 4 in 9% of cycles. Non-haematological toxicity was mild. Tumour response was achieved in 13% of the patients (95% CI 7–20), median survival time was 26 weeks and 1-year survival was 22%. Tumour response to second-line gemcitabine could not be predicted from response to first-line therapy, first-line treatment modality or treatment interval. In a subset of 35 patients HRQL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 questionnaires and showed improvement or control of symptoms and functioning in approximately 30% of patients. We conclude that gemcitabine in second-line treatment has modest anti-tumour activity, is well tolerated, and may control tumour-related symptoms and improve HRQL in a significant minority of patients.

Gemcitabine in the Second-Line Therapy of Patients with Carcinoma of Unknown Primary Site: A Phase II Trial of the Minnie Pearl Cancer Research Network

The purpose of this study was to evaluate the activity ofsingle-agent gemcitabine in previously treated patients with carcinoma ofunknown primary site. Between January 1997 and October 1998, 39 patients wereenrolled in this multicenter Phase II trial performed in the Minnie PearlCancer Research Network. Twenty-seven patients (69%) had adenocarcinoma orpoorly differentiated adenocarcinoma; 35 patients (90%) had previously receivedtreatment with chemotherapy regimens containing both a platinum agent anda taxane. Only 21% of patients had ever responded to previous therapy. Gemcitabine1000 mg/m2 was administered intravenously on days1, 8, and 15 of each 28-day course. Three of 36 evaluable patients (8%) hadpartial responses, and 9 patients (25%) had minor responses or stable diseasewith improved symptoms. The median time to progression for patients with partialresponses or stable disease/improved symptoms was 5 months. Treatment waswell tolerated, with uncommon grade 3 or 4 toxicity. Gemcitabine produceda low objective response rate in this refractory patient population, althoughapproximately one-third of patients experienced symptomatic improvement. Treatmentwith gemcitabine was well tolerated. Because gemcitabine has activity againsta variety of adenocarcinomas, further evaluation of this agent as part offirst-line therapy for patients with carcinoma of unknown primary site isappropriate.