Gemcitabine And Paclitaxel Research Articles

A Novel HRD Signature Is Predictive of FOLFIRINOX Benefit in Metastatic Pancreatic Cancer.

Pancreatic cancer (PC) represents an aggressive disease with median overall survival (OS) of less than 1 year in the front-line setting. FOLFIRINOX and gemcitabine and paclitaxel (GP) are standard of care options for these patients; however, optimal selection of therapy is challenging. Comprehensive genomic profiling was performed on 8358 PC patients. Outcomes were available for 1149 metastatic PC patients treated with 1L FOLFIRINOX or GP. A scar-based measure of HRD was called using a machine learning-based algorithm incorporating copy number and indel features. A scar-based HRD signature (HRDsig) was identified in 9% of patients. HRDsig significantly co-occurred with biallelic alterations in BRCA1/2, PALB2, BARD1, and RAD51C/D, but encompassed a larger population than that defined by BRCA1/BRCA2/PALB2 (9% vs. 6%). HRDsig was predictive of 1L FOLFIRNOX chemotherapy benefit with doubled OS relative to gemcitabine and paclitaxel (GP) (rwOS aHR 0.37 [0.22-0.62]), including 25% of the population with long-term (2 year+) survival in a real-world cohort of patients. Less benefit from FOLFIRINOX was observed in the HRDsig(-) population. Predictive value was seen in both the BRCA1/2/PALB2 mutant and wildtype populations, suggesting additional value to mutational profiling. A scar-based HRD biomarker was identified in a significant fraction of PC patients and is predictive of FOLFIRINOX benefit. Incorporating a biomarker like HRDsig could identify the right patients for platinum chemotherapy and potentially reduce FOLFIRINOX use by over 40%, minimizing toxicities with similar survival outcomes. Confirmatory studies should be performed.

Pembrolizumab Versus Combined Chemotherapy With Gemcitabine and Paclitaxel: A Comparative Assessment of Clinical Outcomes in Patients With Platinum-refractory Advanced Urothelial Cancer.

There are limited data on comprehensive assessments of several treatments as second-line therapy against advanced urothelial cancer (UC). The objective of this study was to compare clinical outcomes between advanced UC patients receiving either pembrolizumab (Pem) or combined chemotherapy with gemcitabine and paclitaxel (GP) as second-line therapy. This study retrospectively analyzed the clinical outcomes of 89 patients with platinum-refractory advanced UC, consisting of 46 and 43 who received Pem and GP therapy, respectively, as second-line treatment. There were no significant differences in major clinicopathological parameters between Pem and GP groups. No significant difference in the objective response rate was noted between the two groups. Progression-free survival (PFS) in the Pem group was significantly longer than that in the GP group; however, there was no significant difference in overall survival (OS) between them. Multivariate analyses identified performance status ≤2 and liver metastasis as independent factors associated with poor outcomes in both PFS and OS. The incidence of adverse events in the GP group was significantly higher than that in the Pem group. Pem could be regarded as standard agent for platinum-refractory advanced UC patients.

Novel drug combination nanoparticles exhibit enhanced plasma exposure and dose-responsive effects on eliminating breast cancer lung metastasis.

Early diagnosis along with new drugs targeted to cancer receptors and immunocheckpoints have improved breast cancer survival. However, full remission remains elusive for metastatic breast cancer due to dose-limiting toxicities of heavily used, highly potent drug combinations such as gemcitabine and paclitaxel. Therefore, novel strategies that lower the effective dose and improve safety margins could enhance the effect of these drug combinations. To this end, we developed and evaluated a novel drug combination of gemcitabine and paclitaxel (GT). Leveraging a simple and scalable drug-combination nanoparticle platform (DcNP), we successfully prepared an injectable GT combination in DcNP (GT DcNP). Compared to a Cremophor EL/ethanol assisted drug suspension in buffer (CrEL), GT DcNP exhibits about 56-fold and 8.6-fold increases in plasma drug exposure (area under the curve, AUC) and apparent half-life of gemcitabine respectively, and a 2.9-fold increase of AUC for paclitaxel. Using 4T1 as a syngeneic model for breast cancer metastasis, we found that a single GT (20/2 mg/kg) dose in DcNP nearly eliminated colonization in the lungs. This effect was not achievable by a CrEL drug combination at a 5-fold higher dose (i.e., 100/10 mg/kg GT). A dose-response study indicates that GT DcNP provided a therapeutic index of ~15.8. Collectively, these data suggest that GT DcNP could be effective against advancing metastatic breast cancer with a margin of safety. As the DcNP formulation is intentionally designed to be simple, scalable, and long-acting, it may be suitable for clinical development to find effective treatment against metastatic breast cancer.

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 ...

Biweekly gemcitabine and paclitaxel in patients with relapsed or metastatic squamous cell carcinoma of the head and neck.

Purpose:We conducted a Phase II, clinical trial to evaluate the efficacy and safety of a biweekly gemcitabine and paclitaxel (GEMTAX) regimen as second-line treatment in patients with recurrent or metastatic unresectable, squamous cell carcinoma of the head and neck (SCCHN). The primary endpoint was response rate.Patients and Methods:Patients with recurrent unresectable or metastatic platinum refractory SCCHN, who had performance status ≤2 and adequate organ function, were eligible. Gemcitabine (3000 mg/m2 intravenous) and paclitaxel (150 mg/m2 intravenous) was given on days 1 and 15of 4 weeks cycle, until patients had disease progression or unacceptable toxicity.Results:Disease control (partial response [PR] + complete response [CR] + stable disease [SD]) was noted in 19 patients (54%) and overall response (CR + PR) was noted in 8 patients (23%). However, the most frequent response outcomes were progressive disease in 16 patients (46%) and SD in 11 patients (31%). The most frequent Grade 3–4 adverse events were lymphopenia in 38 patients (75%), anemia in 20 patients (39%), and infection in 16 patients (31%). Median progression-free survival was 3.6 months; median overall survival was 6.3 months.Conclusion:The biweekly GEMTAX regimen has statistically significant grade 3 and 4 adverse events and has meaningful clinical activity as a second-line treatment in patients with recurrent or metastatic SCCHN who have received prior chemotherapy. This regimen may particularly be a useful treatment option in patients who progressed in less than 6 months of concurrent chemoradiotherapy with high-dose cisplatin and/or have recurrent/metastatic platinum refractory SCCHN.

Phase II trial of biweekly gemcitabine and paclitaxel with recurrent or metastatic squamous cell carcinoma of the head and neck: Southwest Oncology Group study S0329

A phase I study and an institutional pilot study in patients with metastatic/recurrent squamous cell carcinoma of the head and neck (SCCHN) utilizing biweekly gemcitabine and paclitaxel (GEMTAX), showed an overall response rate of 53%. 1 This phase II trial was conducted to determine the feasibility, tolerability, and efficacy of this combination. Patients with metastatic/recurrent SCCHN were treated with gemcitabine (3000 mg/m2) and paclitaxel (150 mg/m2) on days 1 and 15 of every 28-day cycle. In 57 patients with measurable disease, median progression-free survival (PFS) was 4 months and median overall survival (OS) was 8 months. Overall response rate of 28% and disease stabilization in 19% were seen. There were no treatment-related deaths with grade 3/4 hematologic toxicity seen in 20% of the patients. Biweekly GEMTAX is feasible, well tolerated, and demonstrated reasonable efficacy. This may be an alternative for patients who are not candidates for platinum-based chemotherapy.

The effect of gemcitabine/paclitaxel chemotherapy on the survival of patients with metastatic urothelial cancers

To evaluate the survival benefit of gemcitabine and paclitaxel (GT) chemotherapy for patients with metastatic urothelial cancer (UC), a retrospective analysis was performed to compare the overall survival in two periods: before (group I) and after (group II) the introduction of GT chemotherapy. Eighty-five patients with metastatic UC were treated with MEC/MVAC (methotrexate, epirubicin, and cisplatin / methotrexate, vinblastine, doxorubicin, and cisplatin) or GT between 1995 and 2007. The response rate, maintenance rate, maintenance duration of each regimen, and the survival times of responding patients in each group were evaluated retrospectively. The median survival of patients in group ΙI (20months) was significantly longer than that for group I (13months) (p=0.03). Especially in patients with a favorable response (CR/PR) to induction chemotherapy, the median survival period was significantly different between group Ι and group II (median 15 and 28months, respectively; p=0.02). The rate of the shift to maintenance chemotherapy when using GT chemotherapy was significantly higher than with MEC/MVAC chemotherapy alone (p<0.05), and the cessation rate due to adverse effects was significantly lower when using GT chemotherapy (26.1%) than MEC/MVAC in group Ι (42.1%). Our results demonstrated that the administration of GT chemotherapy may be useful to improve the survival of patients with metastatic UC. This effect was significant, especially among those who were sensitive to the induction course of first-line chemotherapy. The excellent tolerability of GT regimens mean that they may be suitable for maintenance chemotherapy.

Prognostic Factors in Second-Line Treatment of Urothelial Cancers With Gemcitabine and Paclitaxel (German Association of Urological Oncology Trial AB20/99)

BackgroundIn the treatment of urothelial cancer, identification of patients who are likely to benefit from further therapy after cisplatin failure is crucial for reasonable treatment decisions. ObjectiveValidate the prognostic factor model (PFM) for survival developed by Bellmunt et al. in a different patient cohort with a different chemotherapy regimen. Design, setting, and participantsBaseline parameters of 102 patients treated within a randomized phase 3 trial of second-line gemcitabine and paclitaxel (GP) comparing short-term to prolonged chemotherapy (German Association of Urological Oncology trial AB20/99) were analyzed. Patients were stratified according to the PFM based on a score including performance status, presence of hepatic metastases, and hemoglobin levels. MeasurementsThe baseline parameters of the GP cohort were compared with those of patients treated in the phase 3 trial of vinflunine versus best supportive care. Univariate and multivariate analyses of baseline parameters with respect to overall survival (OS) and treatment response were performed. OS of patients stratified according to the PFM was compared by log-rank test. Results and limitationsThe vinflunine and the GP cohorts differed, as patients after perioperative (neoadjuvant or adjuvant) treatment were included in the latter cohort. According to the PFM, prognostic subgroups with significant difference in OS (11.8 mo [95% confidence interval (CI), 6.3–17.3], 8.1 mo [95% CI, 4.8–11.4], 3.2 mo [95% CI, 0.0–7.9]; p=0.007) were identified. The PFM identified risk groups in patients with failed treatment of metastatic disease (14.1 mo [95% CI, 8.9–19.3], 7.3 mo [95% CI, 0.0–17.8], 3.8 mo [95% CI, 0.0–9.0]; p=0.006) but not in patients treated (neo)adjuvantly. Lymph node–only disease was a strong predictor of treatment response that overruled every other single predictive parameter (0.284, p=0.0266). ConclusionsThe PFM was successfully validated in the GP and should be used to tailor second-line treatment strategy. Patients with lymph node–only disease may benefit from second-line treatment even if anemia or impaired performance status is present. Trial registrationGerman Cancer Society 01–09 (www.krebsgesellschaft.de).

Prognostic factors in second-line treatment of urothelial cancers with gemcitabine and paclitaxel: German Association of Urological Oncology (AUO) trial AB 20/99.

4586 Background: Clinical response in second-line treatment of urothelial cancers after cisplatin-failure may differ substantially. Progressive disease during treatment with survival of only a few weeks as well as long-term survival of several years is possible. Aim of this analysis was to validate the prognostic model for survival developed by Bellmunt et al. in a different patient-cohort. Methods: Baseline parameters (BPs) of 102 patients (pts.) derived from the largest phase III trial of second-line chemotherapy with gemcitabine and paclitaxel (GP) were compared to the phase III cohort of vinflunine versus best supportive care (n = 370). Uni- and multivariate analyses of BPs with respect to overall survival (OS) were performed. Pts. were stratified according to the Bellmunt model (ECOG > 1, hemoglobin < 10 g/dl, hepatic disease) and altered models. OS of subgroups was compared by log-rank test. Accuracy of the different models to identify subgroups with favorable and poor survival was tested by ROC-analysis. Results: BPs were comparable. The identification of prognostic subgroups by Bellmunt with significant difference in OS could be validated (11.8 [95%CI 6.3-17.3], 8.1 [95%CI 4.8-11.4], 3.2 [95%CI 0.0-7.9] months, P=.007). The prediction of poor (AUC=0.660, P=.023) as well as favorable (AUC=0.634, P=.036) prognosis was possible. A different hemoglobin cut-off value (<12 g/dl) was identified as a poor prognostic factor in a multivariate analysis (HR 1.485, P<.001) and resulted in a better discrimination of pts. OS (14.1 [95% CI 7.5-20.7], 10.9 [95% CI 4.9-16.9], 5.7 [95% CI 4.6-6.8], 3.2 [95% CI 1.5-3.1] months, P<.001). However, apart from the Bellmunt parameters lymph-node-only disease was the strongest predictor of prolonged OS and overruled every other single Bellmunt parameter in a multivariate analysis (HR 0.506, P=.001). Conclusions: The Bellmunt risk factor model was validated in the GP cohort. Lymph-node-only disease was identified as a favorable factor for OS which overrules the prognostic model. Therefore, in these patients every treatment option should be taken into account, even if anemia or impaired performance status is present.

A phase II trial of biweekly gemcitabine and paclitaxel (GEMTAX) combination in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN): A Southwest Oncology Group study.

5555 Background: Combinations of gemcitabine (G) and paclitaxel (P) have documented efficacy in lung, bladder, and breast cancer. Based on prior phase I data and pilot data of this regimen in advanced SCCHN, we conducted a multicenter phase II study to assess the efficacy and safety of biweekly GEMTAX in patients (pts) with recurrent or metastatic SCCHN. Methods: Eligible pts had biopsy proven SCCHN, either metastatic or persistent/recurrent after definitive surgery or radiation therapy. Pts also had Zubrod PS ≤ 1, sensory neuropathy < grade (Gr) 2, no serious organ dysfunction or CNS metastases. One prior induction or adjuvant regimen was allowed, with no G or taxanes, completed at least 6 months prior to enrollment. Treatment was G 3,000 mg/m2 and P 150 mg/m2 on days 1 and 15 of a 28 day cycle. Response to treatment was evaluated every 2 cycles. Treatment continued for 4 cycles after confirmed complete response or until disease progression. Results: 63 eligible pts (50 males, 13 females), median age 63.1 (range 40.7-82.9), were enrolled from 19 SWOG institutions. Major primary sites: 20 lip/oral cavity, 13 oropharynx, and 16 larynx. Status at enrollment: 50 recurrent, 7 persistent, 5 newly diagnosed. Response in 57 pts with measurable disease was 2 complete and 13 partial responses, for an estimated response rate of 26% (95% CI 16-40). The median times to overall and progression free survival were 8 months (95% CI 7-11) and 4 months (95% CI 3-6), respectively. Among 8 pts alive at last contact the median follow-up was 39 months (range 26-54). There were no treatment related deaths. Twelve (19%) patients had Gr 4 events, and 40 (63%) had Gr 3 events, with 8 hematologic events in each of Gr 3 and Gr 4. The most common Gr 3/4 events were fatigue 8 (13%), neutropenia 5 (8%), and neuropathy 4 (6%). Conclusions: GEMTAX appears to have activity similar to other doublets in metastatic and recurrent SCCHN, with somewhat less toxicity. The tolerability and activity, despite lack of a platinum, suggests that biweekly GEMTAX is a useful combination, warranting further study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly

Biweekly Paclitaxel and Gemcitabine for Patients with Advanced Urothelial Cancer Ineligible for Cisplatin-Based Regimen

To avoid cisplatin-related gastrointestinal, renal and other toxicity while maintaining efficacy in the palliative setting or second line chemotherapeutic regimen for cisplatin-resistant urothelial cancer, chemotherapeutic regimens have been investigated that do not include cisplatin. The current study was designed to evaluate efficacy, clinical feasibility and safety of gemcitabine and paclitaxel (GP) regimen in patients with metastatic urothelial cancer who were ineligible for standard cisplatin-based combination chemotherapy. Gemcitabine 2500 mg/m(2) and paclitaxel 150 mg/m(2) were administered intravenously every 2 weeks for 23 patients (17 males and 6 females) with advanced urothelial cancer who were ineligible for cisplatin-based chemotherapy; metastatic disease being resistant to cisplatin-based chemotherapy regimen in 14, heavy toxicity in prior cisplatin-based chemotherapy in three, poor ECOG performance in two and impaired renal function in four. Average age was 67 (53-77). Performance status was 0 in 18 patients, 1 in three patients and 2 in two patients. The overall response rate was 30% (95% CI 15.6-50.8%). Of the 23 patients, no patient attained CR and 7 patients had PR. In the cisplatin-resistant group, the response rate was 14.2% (2/14; 95% CI 4.0-39.9%). In the remaining patients ineligible for cisplatin, the response rate was 55.5% (5/9; 95% CI 26.6-81.1%). The median duration of response was 4 months (range 3-8). The median duration of survival for all patients was 12.1 months (95% CI 8.6-15.5). Myelosuppression, predominantly neutropenia, was the most common serious toxicity and toxicity of Grade 3 or greater was observed in six patients (26%). Among non-hematological toxicity, neuralgia was the most commonly observed and occurred in nine patients (39%) although no patient had toxicity of Grade 3 or greater. Three patients had interstitial pneumonitis possibly attributed to gemcitabine. One patient developed severe bilateral disease after two cycles of the regimen, which was partially resolved with corticosteroid therapy. GP regimen is effective in some patients with cisplatin-resistant urothelial cancer and promising as second line chemotherapy. GP regimen is more effective and well tolerated as first line chemotherapy in patients ineligible for cisplatin-based chemotherapy. Toxicity is generally mild but care must be taken for patients with risk of interstitial pneumonitis. A further larger scale study is required to confirm the efficacy of the GP regimen.

P-204 Mature results of a non-platinum-based [gemcitabine and paclitaxel (GEMPAC)] phase II study in patients (Pts) with advanced non-small cell lung cancer (NSCLC)

P-204 Mature results of a non-platinum-based [gemcitabine and paclitaxel (GEMPAC)] phase II study in patients (Pts) with advanced non-small cell lung cancer (NSCLC)

Phase II trial of gemcitabine and paclitaxel (GEMTAX) combination in recurrent or advanced squamous cell carcinoma of the head and neck

Phase II trial of gemcitabine and paclitaxel (GEMTAX) combination in recurrent or advanced squamous cell carcinoma of the head and neck