Gemcitabine Docetaxel Research Articles

The Combination of Anlotinib and Gemcitabine/Docetaxel in Patients with Metastatic Osteosarcoma Who Have Failed Standard Chemotherapy.

PurposeThe options for the second-line treatment of metastatic osteosarcoma are still limited. Anlotinib is a multi-kinase inhibitor which has shown promising efficacy and good tolerability in various cancer types. This retrospective study was conducted to evaluate the efficacy and safety of anlotinib combined with gemcitabine/docetaxel (GD) in patients with metastatic osteosarcoma who have failed first-line chemotherapy.Patients and MethodsThe data of patients who received anlotinib combined with GD or GD were collected. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate and safety.ResultsFrom July 2013 to November 2020, a total of 32 patients were enrolled, 13 received anlotinib combined with GD and 19 received GD. Median PFS was 9.0 months (95% CI 6.7–39.1) in the combination group and 5.0 months (95% CI 1.2–6.7) in the chemotherapy group. ORR were 38.4% and 15.8%, DCR were 69.2% and 38.1% in the combination and chemotherapy group, respectively. The most common adverse events included fatigue (78.9% in the combination group vs 69.2% in the chemotherapy group), hypertension (46.2% vs 10.5%), diarrhea (38.5% vs 21.1%), hypothyroidism (38.5% vs 15.8%), neutropenia (23.1% vs 36.8%) and AST elevation (30.8% vs 21.1%). The most common grade 3 or worse adverse events included hand-foot reaction (7.7% vs 5.3%), hypothyroidism (15.4% vs 0), neutropenia (0 vs 10.5%).ConclusionThe combination of anlotinib and GD showed favorable efficacy with manageable toxicities compared with GD in the second-line treatment for metastatic osteosarcoma. This combination therapy deserves further investigations in patients with osteosarcoma.

A phase II study of gemcitabine docetaxel combination in metastatic/unresectable locally advanced relapsed synovial sarcoma.

11554 Background: Synovial sarcoma (SS) is one of the commonest non-Rhabdomyosarcoma Soft Tissue Sarcomas (STS) in Adolescent and Young Adults. It is a chemosensitive, high-grade tumor with a tendency for local and metastatic recurrence. While the frontline therapy is doxorubicin, treatment options in later lines are scarce. Gemcitabine docetaxel combination has demonstrated its role in relapsed STS and promising potential in frontline setting in recent times. The major STS types in previous trials included leiomyosarcomas and pleomorphic sarcomas but in SS, this regimen has not been explored. We conducted this study on gemcitabine and docetaxel combination in relapsed metastatic/locally advanced unresectable SS. Methods: This is a phase II, single-arm study in patients (pts) of metastatic/locally advanced unresectable SS relapsed post atleast one line of treatment aged between 15-75 years, ECOG performance status (PS) 0-2, adequate organ function and measurable disease by RECIST 1.1. Treatment was gemcitabine 900 mg/m2 on days 1 and 8 plus docetaxel 75 mg/m2 on day 8 with G-CSF prophylaxis for maximum 6 cycles. Adverse event (AE) profile was analyzed by CTCAE 5.0, quality of life (QoL) assessed 4-weekly by EORTC QLQ-C30 questionnaire and response assessed by RECIST at 12 weeks. Primary endpoint, 3-month Progression-free survival rate (PFR) was required to be 40%. Results: 22 pts were enrolled between 3/2020 – 9/2021 with median age 32 (range 15-60 years); 13 (59%) patients were male; ECOG PS was 1 in 13 (59%) and 2 in 9. Extremity and lung were the commonest primary and metastatic sites respectively with 20 (90.9%) pts having metastases. 50% pts received the study treatment in 2nd line, 36.3% in 3rd line and the remaining in 4th line. The 3-month PFR was 45.4%, median PFS was 3 months, OS 67% at 7 months follow-up and Overall Response Rate (ORR) was 4.5% (1 PR). There was statistically significant worsening in QoL parameters of cognitive functioning, fatigue, dyspnea, appetite loss, nausea/vomiting at 12 weeks. Progression-free pts had better QoL in cognitive and emotional function, fatigue, pain and global health status. Beyond 12 weeks, 7 out of 10 non-progressors continued the treatment (1 patient each discontinued treatment due to death, change to TKI and enrolment in another trial). The most common AEs were fatigue, nausea/vomiting, mucositis, diarrhea, alopecia, anemia, transaminitis; Grade > 3 AEs (31.8%) included anemia, neutropenia, hyperbilirubinemia, transaminitis, mucositis. There was no febrile neutropenia. Conclusions: This is the first prospective study on gemcitabine docetaxel in patients of SS. The trial met its primary endpoint of 3-month PFR more than 40% which is promising in relapsed population. The improved QoL among progression-free pts is encouraging. Gemcitabine docetaxel regimen exhibits efficacy and safety to be considered for use in relapsed SS. Clinical trial information: CTRI/2020/02/023612.

PCN74 Long-Term Cost-Effectiveness of Nadofaragene Firadenovec and Oportuzumab Monatox for Treatment of Bacillus Calmette-Guerin (BCG)-Unresponsive, Non-Muscle Invasive Bladder Cancer (NMIBC)

Nadofaragene firadenovec (NADO) and oportuzumab monatox (OPOR) are new treatments for bladder cancer unresponsive to BCG therapy. To evaluate the long-term cost-effectiveness of NADO and OPOR compared with a hypothetical bladder cancer treatment (HT) in BCG-unresponsive NMIBC in 2 patient populations: those with 1) carcinoma in situ (CIS) ± high-grade Ta/T1 and 2) high-grade Ta/T1 alone (Ta/T1). Pembrolizumab (PEM) was also evaluated in CIS, and gemcitabine ± docetaxel (GEM/DOC) in both populations. A semi-Markov model was developed, employing 3-month cycles over a lifetime horizon, from a healthcare sector perspective. Model inputs were obtained through manufacturer- submitted evidence, systematic literature reviews, and clinical expert opinion. NADO price was based on annual PEM price and OPOR price was a manufacturer provided placeholder price. Primary outcomes, discounted at 3% annually, included total costs (TC), quality-adjusted life years gained (QALY), equal value of life years gained (evLYG), and cost/QALY compared to HT. One-way and probabilistic sensitivity analyses were conducted to evaluate uncertainty. For CIS population: NADO had $308,000 TC, 5.17 QALY, 5.26 evLYG, and $151,000 cost/QALY; OPOR had $310,000 TC, 4.69 QALY, 4.73 evLYG, and $382,000 cost/QALY; PEM had $265,000 TC, 5.04 QALY, 5.12 evLYG, and $114,000 cost/QALY, and GEM/DOC had $172,000 TC, 5.88 QALY, 6.00 evLYG, and dominated HT. For Ta/T1 population: NADO had $302,000 TC, 5.52 QALY, 5.64 evLYG, and $93,000 cost/QALY; OPOR had $302,000 TC, 5.23 QALY, 5.32 evLYG, and $123,000 cost/QALY; and GEM/DOC had $165,000 TC, 5.83 QALY, 5.95 evLYG, and dominated HT. Key uncertainty drivers were probabilities of disease progression to MIBC, NMIBC recurrence beyond 12 months and initial treatment efficacy. NADO and OPOR may provide bladder-sparing therapeutic alternatives for BCG- unresponsive NMIBC patients. Pricing of these drugs will determine whether they are cost effective at commonly accepted thresholds.

Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma.

Simple SummaryGemcitabine-docetaxel chemotherapy is an important regimen for the treatment of soft tissue and bone sarcomas. We aimed to determine if gemcitabine-docetaxel when administered every 14-day would be as effective and less toxic compared to the 21-day schedule. Our study shows that indeed when administered in 14-day schedule gemcitabine-docetaxel chemotherapy results in similar chance of tumor shrinkage and survival yet fewer febrile neutropenia and discontinuation of chemotherapy due to intolerance, compared to 21-day schedule. Therefore, 14-day gemcitabine-docetaxel chemotherapy is safer and can be broadly adopted for the treatment of advanced soft tissue and bone sarcomas.Gemcitabine-docetaxel (G-D) combination is an effective chemotherapy for patients with advanced soft tissue and bone sarcoma, first developed with G administered on days 1 and 8, and D on day 8 every 21 days and later modified to be administered every 14 days in 2012. The 14-day regimen has become increasingly adopted. However, its efficacy and toxicities have not been compared. We identified 161 patients with metastatic or locally advanced soft tissue and bone sarcoma treated with either a 14-day or 21-day regimen within Northern California Kaiser Permanente from 1 January 2017 to 30 July 2020 and compared the outcomes and toxicity profiles of patients treated with the either regimen. Seventy-nine (49%) and 82 (51%) patients received the 14-day and the 21-day regimen, respectively, with similar response rate (22.8% and 15.8%, p = 0.26), median progression-free survival (PFS, 4.0 and 3.2 months, p = 0.15), and median overall survival (OS, 12.6 and 14.7 months, p = 0.55). Subset analysis of the untreated patients (approximately 60% of the entire cohort) as well as the patients with leiomyosarcoma only (approximately 50% of the entire cohort) showed that OS was not significantly different between the two regimens. Febrile neutropenia requiring hospitalization occurred in 10 and one patients (p = 0.006) and intolerance leading to discontinuation of chemotherapy occurred in 12 and two patients (p = 0.006) treated with the 21-day and the 14-day regimens, respectively. CDKN2A deletion/mutation or CDK4 amplification was associated with worse median OS (p = 0.06), while a RB1 deletion/mutation was associated with better median PFS (p = 0.05), and these two genomic alterations were mutually exclusive. Our data demonstrate that, compared to the traditional 21-day G-D regimen, the 14-day G-D regimen is equally effective but safer. In addition, CDKN2A and RB1 pathways play significant role on the outcomes of the patients.

The immune microenvironment and relation to outcome in patients with advanced breast cancer treated with docetaxel with or without gemcitabine

ABSTRACT Preclinical studies suggest that some effects of conventional chemotherapy, and in particular, gemcitabine, are mediated through enhanced antitumor immune responses. The objective of this study was to use material from a randomized clinical trial to evaluate whether patients with preexisting immune infiltrates responded better to treatment with gemcitabine + docetaxel (GD) compared to docetaxel alone. Formalin fixed, paraffin-embedded breast cancer tissues from SBG0102 phase 3 trial patients randomly assigned to treatment with GD or docetaxel were used. Immunohistochemical staining for CD8, FOXP3, LAG3, PD-1, PD-L1 and CD163 was performed. Tumor infiltrating lymphocytes (TILs) and tumor associated macrophages were evaluated. Prespecified statistical analyses were performed in a formal prospective-retrospective design. Time to progression was primary endpoint and overall survival secondary endpoint. Correlations between biomarker status and endpoints were evaluated using the Kaplan–Meier method and Cox proportional hazards models. Biomarker data was obtained for 237 patients. There was no difference in treatment effect according to biomarker status for the whole cohort. In planned subgroup analysis by PAM50 subtype, in non-luminal (basal-like and HER2E) breast cancers FOXP3 was a significant predictor of treatment effect with GD compared to docetaxel, with a HR of 0.22 (0.09–0.52) for tumors with low FOXP3 compared to HR 0.92 (0.47–1.80) for high FOXP3 TILs (Pinteraction = 0.01). Immune biomarkers were not predictive of added benefit of gemcitabine in a cohort of mixed breast cancer subtypes. However, in non-luminal breast cancers, patients with low FOXP3+ TILs may have significant benefit from added gemcitabine.

Correlation of response with progression-free (PFS) and overall (OS) survival in relapsed/refractory Ewing sarcoma (RR-ES): Results from the rEECur trial.

11524 Background: Survival for RR-ES at 5 years remains < 15%, so novel treatments are needed. Almost all Phase II trials for RR-ES use response as the primary outcome measure. It is unclear whether response is a valid surrogate for survival outcomes. Methods: Patients (pts) were eligible if they had RR-ES and were evaluable for imaging response (primary outcome) if they had measurable disease by RECIST 1.1. The randomization was initially between four chemotherapy regimens: topotecan-cyclophosphamide, irinotecan-temozolomide, gemcitabine-docetaxel (GD), high-dose ifosfamide. Response was assessed after 2, 4 (primary) and 6 cycles of therapy and was classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD). PFS and OS were secondary outcomes. Survival from each assessment point by response status was analyzed, by Cox models, with hazard ratios (HR) given for PR v. SD and CR+PR v. SD. Results: From 2015-19, 241 pts with response data were entered. The relationship between response status and PFS and OS is shown in the table (HR < 1.0 indicates better outcome for PR or CR+PR than SD). Both PFS and OS were similar for pts with PR or CR+PR compared to those with SD. OS was inferior for patients with PD (all p < 0.01) (PFS is by definition zero for patients with PD at that timepoint). Small numbers mean CR results are not reliable. Results were consistent across all treatments and between refractory and relapsed disease. At the first interim assessment the GD arm was dropped, with risk ratios for response compared to the other three arms (blinded as still open) of 0.3, 0.5 and 0.5. If a new outcome – disease control (CR+PR+SD) – is defined, the risk ratios are 0.7, 0.8 and 0.7; i.e. still inferior for GD, but less so. Conclusions: Response does not correlate with survival outcomes in RR-ES, so considering PR, or even CR, a success and SD a failure when evaluating treatments may be misleading. We propose PFS as a better primary outcome for future trials and it will be introduced as such in the rEECur trial. Clinical trial information: ISRCTN36453794 . [Table: see text]

252P - Uterine sarcomas in Qatar: Clinico-pathological characteristics and treatment outcome

BackgroundUterine sarcomas (US) are a rare, heterogeneous group of malignancies that have rapid progressive clinical course and poor prognosis. We are reporting a retrospective review of clinico-pathological characteristics and outcome of therapy of these tumors in Qatar. MethodsRetrospective records of 37 patients with US treated in Qatar between January 2010 and December 2016 were reviewed. They were stratified according to the age at diagnosis, menopausal status, ethnic group, pathological subtype of the tumor, grade, stage and treatment modalities (single vs combined modalities; surgical procedure, radiotherapy treatment, adjuvant and palliative chemotherapy. Diagnostic and pathology work was done in one facility. Treatment plan was discussed in MDT. The surgical treatment options were TAH with our without BSO. The chemotherapy we used is Docetaxel Gemcitabine in adjuvant setting as well as palliative treatment for metastatic cases. Radiotherapy was conducted via external beam irradiation followed by brachytherapy. Overall survival (OS) was obtained from the date of diagnosis to the date of death. For the patients who were alive, data was censored on the date of last follow up visit. ResultsFor the reviewed 37 patients, the range of age was 23-64 years old with median age 47 years. LMS are representing the most frequent subtype seen in 15 patients (40%), ESS- 10 (28%), RMS 6 (16%), MMMT 2 (4 %) and non-specified 4 (12%). The stage of the disease at time of diagnosis was 1 in 26%, stage II in 48%, stage III in 11% and stage IV 15%. Total 23 patients underwent surgical resection, 12 patients (53%) simple hysterectomy and 11 (47%) TAH+BSO with LN dissection. 13 patients receivedchemotherapy, in 7 cases as adjuvant, in 4 combined with radiotherapy and in 2 cases as palliative. 13 patient received radiotherapy and brachytherapy. Median follow up time was 42 months. Thorough the time 10 patients died, 18 are still alive and 9 have lost follow up. The Kaplan Maier Curve showed median OS 40 months. Survival rate after one year was 79% and after 3 years 58%. ConclusionsIn this pattern of population where the majority of US presented in early stages (74%), 42% will die within the first 3 years which reflect the need for running big phase 3 trials for optimization of the treatment approaches. Legal entity responsible for the studyAshraf Fadlelseid. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

1734TiP - Pulmonary resectable metastases of osteosarcoma with apatinib and chemotherapy (PROACH): A multi-center phase II randomized clinical trial

BackgroundThe prognosis of osteosarcoma at its metastatic stage remains unchanged over the last several decades. Although 60∼80% first pulmonary recurrences were reportedly to be resectable, it’s surprising that the vast majority of trials to date were designed for metastatic osteosarcoma that were considered inoperable. Apatinib, a VEGFR2 inhibitor, is marked by its superior overall response rate (ORR) of ∼55% compared with other anti-angiogenic agents. Therefore, we aim to assess the efficacy and safety of incorporating apatinib with second-line chemotherapy preoperatively for resectable pulmonary metastatic osteosarcoma, with the intent to shrink the lesions for easier resection and eradicate the micro-metastatic residue using the combination therapy. Trial designThis study is a multicenter, open-label, randomized phase II trial (ClinicalTrials ID: NCT03742193) in which ∼180 participants were to be randomized to an active control arm and an intervention arm in 1:1 ratio. Patients in the intervention arm will receive 250mg apatinib twice daily combined with gemcitabine-docetaxel (GD) regimen before and after the pulmonary metastasectomy, while the control arm will receive gemcitabine-docetaxel (GD) regimen only. Osteosarcoma patients with pulmonary recurrence only, which are potentially resectable at baseline will be recruited in the trial. The primary endpoint is progression-free survival (PFS) and the pre-specified target is an at least 30% decrease of hazard rate of progression in the experimental arm compared with the control arm. Error rate level of the trial was set at an one-sided α value of 0.1 and a power (1-β value) of 0.8, with mid-term assessment for both early efficacy and futility. Secondary objectives are to analyze the effect of the new regimen on overall survival, total resectability, objective response rate, clinical benefit rate, tolerability, as well as the potential predictive biomarker(s). Clinical trial identificationNCT03742193; release date: March 2018. Legal entity responsible for the studyAn IIT trial by Ruijin Hospital, Orthopaedic oncology group. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

An evaluation of monthly maintenance therapy among patients receiving intravesical combination gemcitabine/docetaxel for nonmuscle-invasive bladder cancer

PurposeTo report our experience with sequential maintenance intravesical gemcitabine/docetaxel (GEM/DOCE) for patients with nonmuscle-invasive bladder cancer. Materials and methodsFifty-nine patients who received full GEM/DOCE for nonmuscle-invasive bladder cancer between 2013 and 2018, per the protocol adapted from University of Iowa, were identified and characterized. Patients were treated with 6 weekly instillations of GEM/DOCE and subsequent monthly maintenance installations for those with no evidence of disease at the first surveillance. Student's t test and χ2 test were used to compare continuous and categorical variables as appropriate. For survival analyses, Kaplan-Meier (KM) curves were created to assess disease-free survival (DFS). Overall comparisons of KM survival analysis were conducted using the Wilcoxon test. ResultsAmong all patients, median follow-up was 24 months. Sixty-six percent of patients received ≥2 intravesical induction therapies prior to receiving GEM/DOCE. Thirty-one patients (63%) failed ≥2 induction courses of Bacillus Calmette-Guérin (BCG) before receiving GEM/DOCE. Overall DFS was 49% at 1 year and 29% at 2 years. For patients who failed ≥1 induction courses of BCG, overall DFS was 48% at 1 year and 32% at 2 years. GEM/DOCE appears to be effective for therapy naïve and patients who have failed previous intravesical therapies (P = 0.39). There were 41 (69.5%) patients who had no evidence of disease at the first surveillance and were eligible for maintenance therapy. Among these patients, 24 were managed with observation alone and 17 with monthly maintenance. Median follow-up for observed patients was 36 months and 26 months for patients with maintenance. DFS at 1 year was 42% for observed patients and 81% for patients receiving maintenance (P = 0.04). DFS at 2 years was 32% for observed patients and 59% for patients receiving maintenance therapy (P = 0.45). For maintenance eligible patients who received ≥1 induction courses of BCG, DFS was 42% for observed patients and 81% for patients receiving maintenance therapy at 1 year and 34% for observed patients and 59% for patients receiving maintenance therapy at 2 years. Pathologic stage at recurrence was similar between observed patients and those receiving maintenance (P = 0.83). KM analyses showed greater DFS for patients receiving maintenance therapy compared to observed patients (P = 0.04). ConclusionPatients who demonstrate initial complete response to GEM/DOCE may benefit from maintenance GEM/DOCE.

Patterns of sensitivity to a panel of drugs are highly individualised for undifferentiated/unclassified soft tissue sarcoma (USTS) in patient-derived orthotopic xenograft (PDOX) nude-mouse models

Undifferentiated/unclassified soft tissue sarcoma (USTS) is a recalcitrant disease; therefore, precise individualised therapy is needed. Toward this goal, we previously established patient-derived orthotopic xenograft (PDOX) models of USTS in nude mice. Here, we determined the extent of uniqueness of drug response in a panel on USTS PDOX models from 5 different patients. We previously showed that 3 of the 5 patients were resistant to doxorubicin (DOX) despite DOX being first-line therapy. Two weeks after orthotopic tumour implantation, PDOX mouse models were randomised into five groups: untreated control, DOX, gem-citabine/docetaxel (GEM/DOC), pazopanib (PAZ), temozolomide (TEM). Three PDOX cases were completely resistant to DOX. TEM had high efficacy for 4 USTS PDOX models, including DOX-resistant cases. GEM/DOC and PAZ were effective in three USTS PDOX. One case was completely resistant to TEM. Two cases were completely resistant to PAZ. The results showed the drug sensitivity pattern for each USTS PDOX was highly individualised and that at least one effective drug could be found for each. The PDOX model could be effective in precise individualised drug sensitivity testing which is especially important for heterogeneous cancers such as USTS, and can give the patient a greater chance to be treated with an effective drug.

Adjuvant gemcitabine-docetaxel chemotherapy for stage I uterine leiomyosarcoma: Trends and survival outcomes.

To assess recent trends of administering adjuvant gemcitabine-docetaxel (GD) chemotherapy for Stage I uterine leiomyosarcoma, and to compare disease-free and overall survival between women who received and did not receive adjuvant GD chemotherapy. All patients diagnosed with Stage I uterine leiomyosarcoma in a California-Colorado population-based health plan inclusive of 2006-2013 were included in a retrospective cohort. Adjuvant GD chemotherapy rates, clinico-pathologic characteristics and survival estimates were assessed. Of 111 women with Stage I uterine leiomyosarcoma, 33 received adjuvant GD (median 4cycles), 77 received no chemotherapy, and 1 patient excluded for non-GD chemotherapy. GD-chemotherapy and no-chemotherapy groups were similar with respect to age, stage (IA/IB), uterine weight, mitotic index, body mass index, and Charlson comorbidity score. Non-Hispanic white women were twice as likely to receive adjuvant chemotherapy as non-white or Hispanic women (37.7 vs. 17.1%, P=0.02). The proportion of women receiving adjuvant GD chemotherapy increased from 6.5% in 2006-2008 to 46.9% in 2009-2013 (P<0.001). There was no significance difference in unadjusted Kaplan-Meyer estimated disease-free (P=0.95) or overall survival (P=0.43) between GD-chemotherapy and no-chemotherapy cohorts. Corresponding adjusted Cox proportional hazard ratios for adjuvant GD chemotherapy compared to no chemotherapy were 1.01 (95% confidence interval [CI] 0.57-1.80, P=0.97) for recurrence and 1.28 (95% CI 0.69-2.36, P-0.48) for mortality. Use of adjuvant GD chemotherapy for Stage I uterine leiomyosarcoma has increased significantly in the last decade, despite unclear benefit. Compared to no chemotherapy, 4-6cycles of adjuvant GD chemotherapy does not appear to alter survival outcomes.

Final Results of the Randomized Phase II NorCap-CA223 Trial Comparing First-Line All-Oral Versus Taxane-Based Chemotherapy for HER2-Negative Metastatic Breast Cancer

BackgroundThe purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC). Patients and MethodsIn this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months). ResultsThe DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life. ConclusionAll-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations.

MP06-17 GEMCITABINE PLUS PACLITAXEL AS THIRD LINE CHEMOTHERAPY: A FEASIBLE OPTION FOR METASTATIC UROTHELIAL CARCINOMA PATIENTS

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II1 Apr 2016MP06-17 GEMCITABINE PLUS PACLITAXEL AS THIRD LINE CHEMOTHERAPY: A FEASIBLE OPTION FOR METASTATIC UROTHELIAL CARCINOMA PATIENTS Taku Naiki, Keitaro Iida, Ryosuke Ando, Toshiki Etani, Noriyasu Kawai, Takashi Nagai, Yosuke Sugiyama, Masahiro Kondo, Takehiko Okamura, and Takahiro Yasui Taku NaikiTaku Naiki More articles by this author , Keitaro IidaKeitaro Iida More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Toshiki EtaniToshiki Etani More articles by this author , Noriyasu KawaiNoriyasu Kawai More articles by this author , Takashi NagaiTakashi Nagai More articles by this author , Yosuke SugiyamaYosuke Sugiyama More articles by this author , Masahiro KondoMasahiro Kondo More articles by this author , Takehiko OkamuraTakehiko Okamura More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2178AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is no standard second line treatment for patients with metastatic urothelial carcinoma (mUC) after the failure of platinum based first line chemotherapy. In previous study, we reported the efficacy of gemcitabine docetaxel (GD) combination as a second line treatment strategy for patients with mUC after failure of the first line treatment with platinum based chemotherapy. However, the efficacy of GD was not sufficient to be established as a standard second line treatment. The treatment options are limited for patients who demonstrate good performance status following GC or GD therapy. This study was conducted to evaluate the effectiveness of a combination of gemcitabine and paclitaxel (GP) therapy for patients with mUC that was previously treated with two lines of chemotherapy. METHODS Between January 2006 and May 2015, 91 patients were treated with GD as second line chemotherapy. All had received first line chemotherapy consisting of cisplatin. After the failure of the second line GD therapy, 13 patients received GP therapy as a third line treatment. This consisted of gemcitabine (1000 mg/m2) on days 1, 8, and 15 and paclitaxel (200 mg/m2) on day 1 of each 21 day cycle. All patients were evaluated for toxicity and tumor responses. In addition, quality of life (QOL) was estimated by using the Short Form Health Survey (SF36) questionnaire. We analyzed the efficacy of GP as third line chemotherapy in followup study. RESULTS The median number of GP treatment cycles was 4 (range 2 to 8). The objective response rate was 23.1%. The overall survival in third GP group after the end of second line GD therapy was longer than in untreated group. Univariate and multivariate analyses showed that good performance status was the only prognostic factor for tumor response. Grade 3 treatment related toxicity included neutropenia (77%) and thrombocytopenia (62%), and none of the patients showed grade 4 toxicity. The QOL score after 2 cycles of GP therapy was not significantly decreased compared to the pretreatment scores. CONCLUSIONS GP combination chemotherapy as a third line regimen is a favorable option for patients with metastatic UC. Given the safety and benefit profile including QOL observed in this study, further prospective trials are warranted to evaluate this strategic chemotherapy approach for patients with mUC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e74 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Taku Naiki More articles by this author Keitaro Iida More articles by this author Ryosuke Ando More articles by this author Toshiki Etani More articles by this author Noriyasu Kawai More articles by this author Takashi Nagai More articles by this author Yosuke Sugiyama More articles by this author Masahiro Kondo More articles by this author Takehiko Okamura More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Radiotherapy and gemcitabine-docetaxel chemotherapy in children and adolescents with unresectable recurrent or refractory osteosarcoma.

Few reports have described the treatment outcome of osteosarcoma using radiotherapy. We evaluated the efficacy of radiotherapy and gemcitabine and docetaxel chemotherapy for patients with unresectable recurrent or refractory osteosarcoma. Data from six patients (five male, one female) who received radiotherapy and gemcitabine and docetaxel chemotherapy at the Korea Cancer Center Hospital were retrospectively reviewed. Tumor response was evaluated according to metabolic changes using (18)F-fluorodeoxy-D-glucose-positron emission tomography. The median age of the patients was 15.0 years (range, 14.0-15.8 years). Two patients had single bone lesions, and four had multiple metastatic bone lesions. Patients received a median 3.5 courses of gemcitabine and docetaxel chemotherapy (range, 2-6 courses). The median dose of radiotherapy was 50.0 Gy (range, 46-84 Gy). There were two complete metabolic responses and one partial metabolic response. The objective response rate was 50.0% (3/6). Responses were maintained for 4.6, 6.1 and 13.7 months, respectively. Patients were followed up for a median of 5.8 months (range, 2.7-84.6 months), and the median progression-free survival after this treatment was 3.6 months (range, 1.1-13.7 months). At the time of analysis, two patients were alive, one was lost to follow-up and three had died. Radiotherapy with gemcitabine and docetaxel chemotherapy showed some improvement in cases of refractory tumors or multiple bone metastases. Further studies are needed to investigate the efficacy of newer radiotherapy modalities, as well as to identify new radiosensitizing chemotherapy regimens.

A randomized phase III trial of gemcitabine + docetaxel + bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma (uLMS): A Gynecologic Oncology Group study

Objectives: First-line, fixed dose-rate gemcitabine+docetaxel (GD) achieves an objective response (OR) in 35% of uLMS patients. In some cancers, the addition of bevacizumab (B) to chemotherapy has improved overall survival (OS). The primary objective of this study was to determine whether the addition of B to GD increases progression-free survival (PFS) in patients with metastatic uLMS. Secondary objectives were OR and OS.

Synovial sarcoma: Evaluation of response to treatment with gemcitabin and docetaxel.

10564 Background: Synovial Sarcoma (SS) is one of the more common subtypes of soft tissue sarcomas, comprising 8-10% of this entity. It is well known that SS responds well to adriamycin/ifosfamide (AI) therapies, however responses to gemcitabine/docetaxel (GT) combination have not been well documented, although commonly used in practice. This study aimed to evaluate response to GT in patients with SS. Methods: We retrospectively reviewed medical records of patients diagnosed with SS from 2000 to 2012. All patients had confirmed SS by pathology review. Only patients who were metastatic and treated with GT concurrently were included. Results: The study included 51 patients with metastatic disease who received GT concurrently. Majority of patients were white (69%), with a mean age of 42 years (SD 15) when receiving GT. Median time from initial diagnosis to first metastasis was 15 months. Median overall survival from first metastasis was 2.3 years (95% CI 1.8-3.0 years). The majority of patients (96%) had rec...

P0021 Gemcitabine–docetaxel versus cisplatin–gemcitabine as first-line therapy in patients with metastatic non-small-cell lung cancer

Background The aim of this study was to compare the gemcitabine–docetaxel (GD) combination with the standard cisplatin–gemcitabine (CG) regimen in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) in a phase 3 study. Methods From November 2010 to August 2013, all patients with histologically or cytologically confirmed unresectable TNM stage IIIB or IV NSCLC, no prior chemotherapy, and ECOG performance status of 0–2 were enrolled in this study. Findings Ninety-one patients were enrolled, of whom 45 and 46 were randomised to the GD and CG arms, respectively. Median progression-free survival (PFS) was 6 months in the GD group versus 7 months in the CG group ( p = 0.468), which was not statistically significant. Median overall survival (OS) was similar (11 months) between the two groups. There were also no differences in PFS and OS between the two treatment arms with regards to the primary stratification factor of histology ( p = 0.328 and p = 0.202, respectively). No complete response cases were recorded in either group. The partial response rate was 43.5% in the GD group compared with 46.7% in the CG group. Chemotherapy-related toxicities were more common in the CG group. There were no toxicity-related deaths. Interpretation The results presented in this study suggest that the GD combination is as active as the standard CG regimen when used as first-line therapy in the treatment of patients with stage IIIB/IV NSCLC. The more favourable toxicity profile of GD supports its use as first-line chemotherapy, especially in patients who cannot tolerate cisplatin.

A Pooled Analysis of Gemcitabine Plus Docetaxel Versus Capecitabine Plus Docetaxel in Metastatic Breast Cancer

In two randomized phase III trials of patients with metastatic breast cancer (MBC), gemcitabine-docetaxel (GD) and capecitabine-docetaxel (CD) had similar efficacy, but distinct safety profiles. Methods. Data from two GD versus CD studies were pooled; overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were determined. Cox proportional hazards models identified prognostic factors associated with improved OS and PFS. Using a multivariate prognostic model incorporating identified adverse prognostic factors, we grouped MBC patients into low-, intermediate-, and high-risk categories. Hazard ratios (HRs) of GD over CD for OS and PFS were determined for subsets of patients. Results. Baseline demographics of the pooled population were mostly well balanced. In the pooled population, there were no significant differences between GD versus CD for OS (HR = 1.02; p = .824), PFS (HR = 1.15; p = .079), and ORR (p = .526). In the pooled crossover population, there were trends toward improved OS (HR = 0.82; p = .171) and PFS (HR = 0.93; p = .557) with GD. Several prognostic factors (including prior adjuvant taxane) for improved OS or PFS were identified; however, there were no significant interactions between treatment arms and prognostic factors for PFS or OS, except number of metastatic sites. In the prognostic model, median OS and PFS were numerically lower in the high-risk group versus the intermediate- and low-risk groups. Conclusion. This analysis confirms the lack of efficacy difference between GD and CD in the pooled population, crossover population, and almost all subpopulations. Several prognostic factors were associated with improved outcomes in the pooled population.

Gemcitabine and Docetaxel for Metastatic Soft Tissue Sarcoma - a Single Center Experience

Background: Prognosis and survival for patients with metastatic soft tissue sarcoma (STS) are dismal. Standard first-line systemic chemotherapy is anthracycline-based. Gemcitabine/docetaxel (GD) is a therapeutic option in the second-line setting. Here we present the data of our single center retrospective analysis, using GD in locally advanced or metastatic disease. Patients and Methods: Between 2005 and 2012, a total of 34 patients were identified. The majority of tumors were located in the extremities (19/34, 56%) and abdomen/retroperitoneum (10/34, 29%). Most frequent histologies included leiomyosarcoma (13/34, 38%), liposarcoma (7/34, 21%), and pleomorphic sarcoma (6/34, 18%). Results: Objective response to treatment by RECIST criteria after 3 cycles was low with 6% partial responses (PR, 2/34), 65% stable disease (SD, 22/34), and 29% progressive disease (PD, 10/34). Progression-free survival at 3 and 6 months was 77 and 62%, respectively. Patients with a clinical benefit (defined as PR or SD after the 3rd treatment cycle) had a significantly prolonged median progression-free and overall survival with 8.6 months (p < 0.0001; hazard ratio (HR) 33.1) and 22.4 months (p < 0.0001; HR 12.9), respectively. Most common toxicities included hand-foot syndrome, edema, pancytopenia, febrile neutropenia, and mucositis. Conclusion: Overall, we conclude that GD is an active second-line regimen in metastatic STS, with manageable side effects.

P2-127 - Pneumocystis Pneumonia in Patients with Solid Tumors during Chemotherapy

ABSTRACT Background Pneumocystis pneumonia (PCP) is an opportunistic infection well recognized in patients with profound T cell immunodeficiency, especially in patients with AIDS. This infection is also a life-threatening complication seen during immunosuppressive chemotherapy for cancer or organ transplantation, so it is important to make an early diagnosis and start treatment. We present three cases of PCP developing during chemotherapy for solid malignancies. Case reports Case 1: A 50-year-old female received a first-line chemotherapy of gemcitabine–docetaxel (GT therapy) for leiomyosarcoma. After three cycles of GT therapy, she was admitted for a non-productive cough and high fever. Her chest radiograph and CT showed diffuse ground-glass bilateral opacities. SpO2 was 90% (room air). Serum b- d -glucan was 66.7 pg/ml. PCR of PCP by using BAL specimens was positive. We diagnosed PCP infection. Case 2: A 70-year-old female received gemcitabine (GEM) monotherapy as a first-line treatment of a pancreas cancer. After two cycles of GEM therapy, she developed dyspnea and a fever of 38°C. Her chest radiograph and CT showed diffuse ground-glass bilateral opacities. SpO2 was 92% (room air). Serum b- d -glucan was 40.8 pg/ml. We diagnosed PCP infection on the basis of these findings. Case 3: A 64-year-old female received neo-adjuvant chemotherapy with 5-fluoropyrimidine, epirubicin and cyclophosphamide (FEC therapy) for a breast cancer. After two cycles of FEC therapy, she was admitted for febrile neutropenia. Although neutropenia was recovered, she developed exertional dyspnea and a non-productive cough with continuous high fever. Her chest CT showed diffuse ground-glass bilateral opacities. SpO2 was 90% (room air). Serum b- d -glucan was 39.5 pg/ml. We diagnosed PCP infection on the basis of these findings. These patients were immediately treated with trimethoprim–sulfamethoxazole (ST) and corticosteroid. The infiltrations and diffuse ground-glass opacities on their chest radiographs improved and they got well. Conclusion We should be careful of not only drug-induced interstitial pneumonia and febrile neutropenia but also PCP during chemotherapy for solid malignancies.