Gemcitabine-containing Regimens Research Articles

Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Expressing Biliary Tract Cancer (HERB; NCCH1805): A Multicenter, Single-Arm, Phase II Trial.

Treatment options for patients with unresectable or recurrent biliary tract cancer (BTC) who progress on a gemcitabine-containing regimen are limited. In addition, the significance of anti-human epidermal growth factor receptor 2 (HER2) therapy in HER2-expressing BTC has not been sufficiently investigated. In this phase II trial, participants from five institutions in Japan were enrolled. Eligible patients had pathologically confirmed unresectable or recurrent BTC with centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ or IHC2+ and in situ hybridization [ISH]+) or HER2-low (IHC2+ and ISH-, IHC1+, and IHC0 and ISH+) and were refractory or intolerant to a gemcitabine-containing regimen. The patients received 5.4 mg/kg trastuzumab deruxtecan (T-DXd) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the confirmed objective response rate (ORR) in HER2-positive BTC by an independent central review (threshold ORR, 15%; expected ORR, 40%). A total of 32 patients were enrolled and treated. Among these patients, 22 with HER2-positive disease comprised the primary efficacy population and had a confirmed ORR of 36.4% (90% CI, 19.6 to 56.1; P = .01), meeting the primary end point. Eight with HER2-low disease comprised the exploratory population and had a confirmed ORR of 12.5%. The most common ≥grade 3 treatment-related adverse events were anemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease (ILD), including two grade 5 events. T-DXd showed promising activity in patients with HER2-positive BTC and a signal of efficacy in patients with HER2-low BTC. Although the safety profile was generally manageable, ILD requires careful monitoring and early intervention.

The experience of relapsed Burkitt lymphoma treatment with targeted drugs and autologous/allogeneic stem cell transplantation

The use of high-effective, multicomponent, risk-adopted chemoimmunotherapy schemes in children with Burkitt lymphoma reached advanced long-term progression-free survival over 90 % even for high risk patients. Unfortunately, conventional therapeutic strategy for relapsed/refractory disease is not accepted, and the effectiveness of carboplat‑in- and gemcitabine-containing regimens is unsatisfactory. Clinical experience of rituximab, ibrutinib and nivolumab in combination with polychemotherapy and own clinical case of successful relapsed Burkitt lymphoma treatment with targeted therapy and following autologous and allogeneic hematopoietic stem cell transplantation are presented. Proposed program could achieve a complete remission of Burkitt lymphoma, but short-term after allogeneic hematopoietic stem cell transplantation diagnosed T-cell precursor acute lymphoblastic leukemia became fatal for the patient.

Treatment Effect and Safety of Nanoliposomal Irinotecan with Fluorouracil and Folinic Acid after Gemcitabine-Based Therapy in Patients with Advanced Pancreatic Cancer: A Multicenter, Prospective Observational Study.

Although the combination of nanoliposomal irinotecan plus fluorouracil/folinic acid (nal-IRI/FF) exhibited survival benefits in gemcitabine-refractory patients with advanced pancreatic cancer (APC) in the phase III NAPOLI-1 trial, there is limited data on the efficacy and safety of this regimen in real-world settings in Japan. This multicenter, prospective observational study enrolled patients with APC who received nal-IRI/FF after a gemcitabine-based regimen from July 2020 to June 2021. We collected and analyzed clinical data and conducted survival and multivariate analyses. Thirty-one (78%) of the 40 patients had metastases. Nal-IRI/FF was the second-line therapy in 36 patients (90%). The median duration was 3.2 months. The disease control rate was 57%. The median progression-free survival and overall survival (OS) were 4.5 months (95% confidence interval [CI]: 2.8–5.5) and 7.4 months (95% CI: 5.1–10.6), respectively. Common ≥grade 3 toxicities included neutropenia (28%) and fatigue (23%). Fatigue led to treatment discontinuation in 6 out of 10 patients. Multivariate analysis showed that a neutrophil-to-lymphocyte ratio > 4 was a significant risk factor for a short OS (hazard ratio (HR) = 3.08, 95% CI: 1.21–7.85, p = 0.02). In conclusion, nal-IRI/FF is an appropriate treatment option for APC following gemcitabine-containing regimens.

Isocitrate Dehydrogenase-Mutated Cholangiocarcinoma: Natural History and Clinical Outcomes.

Clinical-pathologic features and natural history of patients with isocitrate dehydrogenase (IDH)-mutant intrahepatic cholangiocarcinoma (CCA) are not well characterized. Here, we sought to describe the natural history, clinical phenotype, and prognostic impact of advanced, IDH-mutated CCA. We conducted a multicentric, retrospective analysis of patients with IDH-mutated (IDH1 or IDH2) CCA between 2010 and 2020. Median overall survival (OS) and progression-free survival (PFS) analyses were performed using the Kaplan-Meier method. Chi-square test was used to analyze disease control rate (DCR) and overall response rate (ORR). Matched controls were used for comparing survival between patients with and without IDH mutations (mIDH). Sixty-five patients with IDH-mutated CCA were included. All patients had intrahepatic CCA. On first-line chemotherapy, median OS and median PFS were 21.2 months and 8.3 months, respectively. Notably, median OS (32.4 v 19.5 months, P = .12) and PFS (18.0 v 8.0 months, P = .12) were not significantly affected by disease status at presentation (locally advanced v metastatic, respectively). Median OS was significantly longer in patients with mIDH (21.2 v 10.5 months; P < .01). First-line gemcitabine-containing regimens had a significantly higher DCR and ORR than non-gemcitabine-containing regimens (DCR: 75% v 33%, P = .01; ORR: 39% v 0%, P = .02). In patients receiving IDH inhibitor therapy, median PFS was 4.6 months with a DCR of 29%. CCA with mIDH confers a unique subtype resulting in a better survival compared with that of counterparts. IDH inhibitors represent a promising therapeutic option in later lines of therapy in this subgroup.

A Simplified Geriatric Assessment (sGA) Can Identify Older Patients with Relapse/Refractory (R/R) Aggressive Lymphoma Suitable for Autologous Stem Cell Transplantation (ASCT): Final Results of Recanz Multicentre Prospective Phase 2 Study By the Fondazione Italiana Linfomi (FIL)

A Simplified Geriatric Assessment (sGA) Can Identify Older Patients with Relapse/Refractory (R/R) Aggressive Lymphoma Suitable for Autologous Stem Cell Transplantation (ASCT): Final Results of Recanz Multicentre Prospective Phase 2 Study By the Fondazione Italiana Linfomi (FIL)

Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study

Treatment options are sparse for patients with advanced cholangiocarcinoma after progression on first-line gemcitabine-based therapy. FGFR2 fusions or rearrangements occur in 10-16% of patients with intrahepatic cholangiocarcinoma. Infigratinib is a selective, ATP-competitive inhibitor of fibroblast growth factor receptors. We aimed to evaluate the antitumour activity of infigratinib in patients with locally advanced or metastatic cholangiocarcinoma, FGFR2 alterations, and previous gemcitabine-based treatment. This multicentre, open-label, single-arm, phase 2 study recruited patients from 18 academic centres and hospitals in the USA, Belgium, Spain, Germany, Singapore, Taiwan, and Thailand. Eligible participants were aged 18 years or older, had histologically or cytologically confirmed, locally advanced or metastatic cholangiocarcinoma and FGFR2 fusions or rearrangements, and were previously treated with at least one gemcitabine-containing regimen. Patients received 125 mg of oral infigratinib once daily for 21 days of 28-day cycles until disease progression, intolerance, withdrawal of consent, or death. Radiological tumour evaluation was done at baseline and every 8 weeks until disease progression via CT or MRI of the chest, abdomen, and pelvis. The primary endpoint was objective response rate, defined as the proportion of patients with a best overall response of a confirmed complete or partial response, as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors, version 1.1. The primary outcome and safety were analysed in the full analysis set, which comprised all patients who received at least one dose of infigratinib. This trial is registered with ClinicalTrials.gov, NCT02150967, and is ongoing. Between June 23, 2014, and March 31, 2020, 122 patients were enrolled into our study, of whom 108 with FGFR2 fusions or rearrangements received at least one dose of infigratinib and comprised the full analysis set. After a median follow-up of 10·6 months (IQR 6·2-15·6), the BICR-assessed objective response rate was 23·1% (95% CI 15·6-32·2; 25 of 108 patients), with one confirmed complete response in a patient who only had non-target lesions identified at baseline and 24 partial responses. The most common treatment-emergent adverse events of any grade were hyperphosphataemia (n=83), stomatitis (n=59), fatigue (n=43), and alopecia (n=41). The most common ocular toxicity was dry eyes (n=37). Central serous retinopathy-like and retinal pigment epithelial detachment-like events occurred in 18 (17%) patients, of which ten (9%) were grade 1, seven (6%) were grade 2, and one (1%) was grade 3. There were no treatment-related deaths. Infigratinib has promising clinical activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic cholangiocarcinoma harbouring FGFR2 gene fusions or rearrangements, and so represents a potential new therapeutic option in this setting. QED Therapeutics and Novartis.

Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series.

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

Zanidatamab (ZW25) in HER2-positive biliary tract cancers (BTCs): Results from a phase I study.

299 Background: Treatment options are limited for patients with unresectable, locally advanced or metastatic BTCs progressing after first line treatment. Standard second line chemotherapy yields objective response rates (ORR) of &lt; 10% and median overall survival of these patients is &lt; 6 months. Human epidermal growth factor receptor 2 (HER2) overexpression/ amplification is observed in 5–19% of BTCs. Zanidatamab is a bispecific HER2-targeted antibody that has demonstrated durable single agent activity with good tolerability in a range of HER2-overexpressing cancers. Methods: In the expansion cohort of this phase I study (NCT02892123), the primary objective is to characterize safety and tolerability of zanidatamab and secondary objectives include evaluation of anti-tumor activity. This cohort includes BTC patients with centrally confirmed HER2 overexpression (immunohistochemistry [IHC] 3+ or IHC 2+/ fluorescence in situ hybridization [FISH]+), disease progression after standard of care therapy, and measurable disease per RECIST 1.1. Zanidatamab is administered at the previously identified recommended dose of 20 mg/kg every 2 weeks (Q2W). Tumors are assessed every 8 weeks (response confirmed at ≥ 4 weeks). Results: As of the data cutoff date (Jul 28, 2020), 20 patients (median age: 63 years [range, 42–78]) with BTC (11 gallbladder cancers, 5 intra- and 4 extra-hepatic cholangiocarcinomas) have been treated with zanidatamab. The median number of prior systemic therapies was 2.5 (range, 1–8), including five patients who had received prior HER2-targeted therapy (trastuzumab). Fourteen (70%) patients experienced zanidatamab-related adverse events (AEs), all of which were grade 1 or 2 in severity. The most common (occurring in ≥ 20%) zanidatamab-related AEs were diarrhea (n = 9) and infusion-related reactions (n = 6). A single treatment-related serious AE of grade 2 fatigue was reported in one patient. Among patients evaluable for response (n = 17), the confirmed ORR was 47% (n = 8; 95% confidence interval [CI]: 23, 72), the disease control rate was 65% (n = 11; 95% CI: 38, 86) and the median duration of response was 6.6 months (95% CI: 3.2, not estimable). Conclusions: Zanidatamab is well tolerated with promising and durable anti-tumor activity in patients with HER2 overexpressing BTC. Based on these data, zanidatamab is now being evaluated in an ongoing global Phase 2b study in patients with advanced HER2+ BTC that have progressed after treatment with a gemcitabine-containing regimen (NCT04466891). Clinical trial information: NCT02892123.

Abstract B36: Maintenance chemotherapy after chemoradiation in patients with locally advanced pancreatic cancer

Abstract Background: More than half of patients (pts) with pancreatic cancer (PC) initially present with unresectable, locally advanced disease (LAPC). Data on management of these pts after systemic chemotherapy are scarce. Many clinicians utilize a strategy of induction chemotherapy followed by consolidative concurrent chemoradiation (CRT) for pts not progressing on initial chemotherapy. How to manage pts after CRT is controversial. We sought to evaluate the role of maintenance chemotherapy (MCT) after CRT in pts with LAPC. Methods: We retrospectively analyzed LAPC pts treated with CRT at MD Anderson from 2005-2018. Pts who were taken for curative-intent surgery were excluded. Primary and secondary outcomes were median progression-free survival (mPFS) and median overall survival (mOS), respectively, as measured from the start date of CRT. Data were also obtained on pt demographics, response, and duration of induction chemotherapy as well as MCT regimens. Results: We included 165 pts with LAPC treated with CRT in our analysis. Median age was 66 (range 39 – 84), and 97 (59%) pts were male. Median follow-up was 12.9 months. The median duration from initiation of induction chemotherapy to start of CRT was 4.4 months. Most pts (84%) received 1 line of induction chemotherapy prior to CRT. Ten pts (6%) did not receive induction chemotherapy and 17 pts (10%) received at least 2 lines prior to CRT. All but 9 pts (94%) developed disease progression (PD) after CRT, and 49 pts (33%) had PD within 3 months of CRT. On univariate analysis, PD on the induction chemotherapy regimen immediately prior to CRT was associated with shortened PFS (HR 2.46, p &amp;lt; 0.001) and OS (HR 2.96, p &amp;lt; 0.001) after CRT. Most pts (78%) did not receive MCT after CRT. 69% of pts who received MCT were male, compared to 56% of those who did not receive MCT. The percentages of pts who had PD on the chemotherapy regimen immediately prior to CRT in the MCT and no-MCT groups were 9% and 12%, respectively. Sixteen pts who received MCT were treated with either gemcitabine alone or a gemcitabine-containing regimen, while 14 pts received capecitabine monotherapy. On univariate analysis, the use of MCT after CRT was associated with prolonged mPFS (9.0 vs. 4.2 months, p = 0.01), but was not associated with an increase in mOS (15.5 vs. 12.5 months, p = 0.14). On multivariable analysis controlling for race, radiation dose, age, and whether there was progression on the chemotherapy regimen prior to CRT, the use of MCT was significantly associated with both prolonged PFS (HR 0.45, p &amp;lt; 0.001) and OS (HR 0.66, p = 0.047). Conclusions: In this single-institution retrospective analysis of 165 pts with LAPC treated with CRT, treatment with post-CRT MCT was associated with a significant improvement in both PFS and OS as measured from the start date of CRT. Based on these results, MCT may be an appropriate option for pts with LAPC who have not progressed following consolidative CRT, and a prospective trial should be performed to better address this knowledge gap. Citation Format: Jonathan D. Mizrahi, Shalini Moningi, Graciela M. Nogueras-Gonzalez, Robert A. Wolff, Milind M. Javle, Gauri R. Varadhachary, Linus Ho, David R. Fogelman, Kanwal P. Raghav, Michael J. Overman, Christopher H. Crane, Joseph M. Herman, Albert C. Koong, Eugene J. Koay, Jane E. Rogers, Shubham Pant. Maintenance chemotherapy after chemoradiation in patients with locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B36.

High Complete Response Rate Observed with Second-Line Chemo-Immunotherapy with Pembrolizumab and GVD (Gemcitabine, Vinorelbine, and Liposomal Doxorubicin) in Relapsed and Refractory Classical Hodgkin Lymphoma

High Complete Response Rate Observed with Second-Line Chemo-Immunotherapy with Pembrolizumab and GVD (Gemcitabine, Vinorelbine, and Liposomal Doxorubicin) in Relapsed and Refractory Classical Hodgkin Lymphoma

Antibiotic therapy augments the efficacy of gemcitabine-containing regimens for advanced cancer: a retrospective study.

BackgroundThe addition of antibiotics reportedly augments the efficacy of gemcitabine (GEM) in tumor-bearing mice. However, whether this phenomenon is also observed in cancer patients remains unclear. In the present study, we aimed to assess whether antibiotics for treatment or prevention of infection augments treatment efficacies of GEM-containing regimens in patients with any type of cancer.MethodsMedical records of patients diagnosed with cancer histopathologically and treated with GEM-containing regimens (n=169) were retrospectively reviewed. Patients were assigned into two groups: antibiotics-untreated group (patients who were treated with GEM-containing regimens but without antibiotics) and antibiotics-treated group (patients who were treated with GEM-containing regimens plus antibiotics). Response rates, progression-free survival (PFS) time, and overall survival (OS) time were analyzed for each group.ResultsThe response rates of the antibiotics-untreated and antibiotics-treated groups with GEM-containing regimens were 15.1% and 27.6%, respectively. The median PFS times of the antibiotics-untreated and antibiotics-treated groups were 2.5 (95% CI: 1.86–3.73) and 4.9 (95% CI: 3.47–6.0) months, respectively. The median OS times of the antibiotics-untreated and antibiotics-treated groups were 7.53 (95% CI: 5.63–9.57) months and 13.83 (95% CI: 10.83–16.43) months, respectively.ConclusionThe addition of antibiotics augments the treatment efficacies of GEM-containing regimens, and it may be a potential therapeutic option to improve treatment efficacies of GEM-containing regimens in patients with advanced cancer.

How do gemcitabine-containing dual chemotherapy regimens compare with gemcitabine alone for people with advanced pancreatic cancer?

How do gemcitabine-containing dual chemotherapy regimens compare with gemcitabine alone for people with advanced pancreatic cancer?

RRM1 expression and the clinicopathological characteristics of patients with non-small cell lung cancer treated with gemcitabine.

BackgroundThe usefulness of ribonucleotide reductase catalytic subunit M1 (RRM1) for predicting the therapeutic effects of gemcitabine-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. RRM1-positive patients show unique clinicopathological features.MethodsHere, we performed a meta-analysis to systematically evaluate the relationship between RRM1 expression and the clinicopathological characteristics of NSCLC patients treated with gemcitabine-containing regimens. A comprehensive electronic and manual search was performed to identify relevant articles. The pooled relative risk (RR) and 95% CI were used to estimate the relation between the clinicopathological characteristics of NSCLC patients and RRM1 expression.ResultsThe study included 31 observational studies and 3,667 patients. The analysis showed no significant association between RRM1 expression and pathological type, stage, and smoking status; however, RRM1 positivity was significantly lower in women than in men (43.0% vs 51.7%, RR=0.84, 95% CI: 0.74–0.94, P=0.004).ConclusionThe present pooled analyses demonstrated that RRM1 positivity in women with advanced NSCLC was associated with a higher rate of response to gemcitabine-containing regimens. Immunohistochemistry may be valuable to prescreen for RRM1 expression in clinical practice, whereas PCR can be routinely used as a verification method. These findings will help design suitable molecular-targeted therapies for NSCLC.

SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting

Background:We investigated selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective, allosteric MEK1/2 inhibitor, plus platinum-doublet chemotherapy for patients with advanced/metastatic non-small cell lung cancer.Methods:In this Phase I, open-label study (NCT01809210), treatment-naïve patients received selumetinib (50, 75, 100 mg BID PO) plus standard doses of gemcitabine or pemetrexed plus cisplatin or carboplatin. Primary objectives were safety, tolerability, and determination of recommended Phase II doses.Results:Fifty-five patients received treatment: selumetinib 50 or 75 mg plus gemcitabine/cisplatin (n=10); selumetinib 50 mg plus gemcitabine/carboplatin (n=9); selumetinib 50, 75 or 100 mg plus pemetrexed/carboplatin (n=21); selumetinib 75 mg plus pemetrexed/cisplatin (n=15). Most frequent adverse events (AEs) were fatigue, nausea, diarrhoea and vomiting. Grade ⩾3 selumetinib-related AEs were reported in 30 (55%) patients. Dose-limiting toxicities (all n=1) were Grade 4 anaemia (selumetinib 75 mg plus gemcitabine/cisplatin), Grade 4 thrombocytopenia/epistaxis and Grade 4 thrombocytopenia (selumetinib 50 mg plus gemcitabine/carboplatin), Grade 4 febrile neutropenia (selumetinib 100 mg plus pemetrexed/carboplatin), and Grade 3 lethargy (selumetinib 75 mg plus pemetrexed/cisplatin). Partial responses were confirmed in 11 (20%) and unconfirmed in 9 (16%) patients.Conclusions:Standard doses of pemetrexed/carboplatin or pemetrexed/cisplatin were tolerated with selumetinib 75 mg BID. The selumetinib plus gemcitabine-containing regimens were not tolerated.

The advantage of pemetrexed combined with platium chemotherapy treatement for advanced nonsquamous non-small-cell lung cancer (NSCLC) patients without drive oncogene.

e20527 Background:Platinum-based chemotherapy is the standard first-line treatment for non-squamous NSCLC patients without driver oncogene (EGFR, KRAS, and ALK mutations). However, it remains unknown that from which chemotherapy regimens can those patients get more benefit. Therefore, the study explore whether pemetrexed combined with platinum chemotherapy is superior to the other platinum-based chemotherapy regimens.Methods:We performed a retrospective study on 114 histologically or cytologically advanced IIIB-IV NSCLC patients admitted to Cancer Hospital from 1 Jan 2013 to 30 Dec 2015. The primary endpoint was the median progression free survival (PFS) and the disease control rate (DCR). And objective response was evaluated every two cycles by imaging according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). The multivariate logistic analyses were carried out by SPSS version 16.0. Results:114 patients received platinum-base doublet as first-line treatment. Among them, 59 patients underwent pemetrexed-containing regimens, and 55 patients received non-pemetrexed-containing regimens (38 patients for paclitaxel-containing regimens, 13 patients for gemcitabine-containing regimens, and 4 patients for other regimens.). The baseline characteristics between two groups were comparable ( p&gt;0.05). The median PFS of pemetrexed-containing regimens was significantly longer compared with that of non-pemetrexed-containing regimens (7.2 months [95% CI: 5.3–9.1] vs. 4.9 months [95% CI: 3.2–6.6], p%0.05). DCR of pemetrexed-containing regimens was better than that of non-pemetrexed-containing regimens in the multivariate logistic analysis (89.8% vs.74.5%, p%0.05).Conclusions:Pemetrexed-containing regimens displayed more benefit than the other chemotherapy regimens for non-squamous NSCLC patients without driver oncogene. However, large scale perspective study is warranted in the future.

A prospective cohort study of patients with peripheral T-cell lymphoma in the United States.

Long-term survival in patients with aggressive peripheral T-cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States. Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) is a prospective multicenter cohort study designed to identify the most common prevailing treatment patterns used for patients newly diagnosed with PTCL in the United States. Patients with nodal PTCL and completed records regarding baseline characteristics and initial therapy were included in this analysis. All statistical tests were 2-sided. Of a total of 499 patients enrolled, 256 (51.3%) had nodal PTCL and completed treatment records. As initial therapy, patients received doxorubicin-containing regimens (41.8%), regimens containing doxorubicin plus etoposide (20.9%), other etoposide regimens (15.8%), other single-agent or combination regimens (19.2%), and gemcitabine-containing regimens (2.1%). Survival was found to be statistically significantly longer for patients who received doxorubicin (log-rank P = .03). After controlling for disease histology and International Prognostic Index, results demonstrated a trend toward significance in mortality reduction in patients who received doxorubicin compared with those who did not (hazard ratio, 0.71; 95% confidence interval, 0.48-1.05 [P = .09]). To the authors' knowledge, there is no clear standard of care in the treatment of patients with PTCL in the United States. Although efforts to improve frontline treatments are necessary, anthracyclines remain an important component of initial therapy for curative intent. Cancer 2017;123:1174-1183. © 2016 American Cancer Society.

Prognostic factor for overall survival in the "difficult-to-treat" germ cell tumor patients.

402 Background: Our previous observation showed germ cell tumor (GCT) patients who finished at first-, second- or third-line chemotherapy obtained good overall survival. On the other hand, patients with 4th line-or-after chemotherapy showed much poorer outcome. The aim of this study was to investigate the prognostic factor for overall survival in the patients with 4th-line-or-after chemotherapy. Methods: Between August 1998 and December 2013, seventy-four GCT patients had 4th line-or-after chemotherapy at our institution. These patients were defined as ‘difficult-to-treat’ GCT patients in this study. We retrospectively assessed clinical and therapeutic parameters. Median age was 33 y.o.(range;19-55). Nonseminoma was found in 86.5%. Good, intermediate and poor prognosis by IGCCC was 23, 17 and 26 cases, respectively. With regard to IGCCC at salvage, very low, low, intermediate, high and very high was 2, 7, 10, 18 and 6 cases, respectively. Results: Fiver-year overall survival was 55.6%. Choice of 2nd line or 3rd line chemotherapy did not influence overall survival, for example, VeIP (vinblastine, ifosfamide, cisplatin) or VIP (etoposide, ifosfamide, cisplatin) versus other chemotherapy as 2nd line therapy (5-y OS; 55.2% and 56.3%, log-rank, p=0.78). The identical result was observed in paclitaxel-containing therapy such as TIP versus other chemotherapy (paclitaxel, ifosfamide, cisplatin) (5-y OS; 52.8% and 57.1%, log-rank, p=0.90). In the choice of 4th line chemotherapy, gemcitabine-containing regimen was not superior to other chemotherapy (5-y OS; 57.0% and 55.3%, log-rank, p=0.98). Statistical significant parameters were primary site, IGCCC at salvage, required chemotherapy line and serum tumor marker (STM) normalization by univariate analysis. Multivariate analysis showed independent prognostic factor for overall survival was normalization of serum tumor marker during chemotherapy (Hazard Ratio;0.12, 95% Confidence Interval;0.02-0.62, p=0.01). Conclusions: STM normalization is thought to be mandatory for overall survival in the management of ‘difficult-to-treat’ advanced GCT patients.

Incidence of hematologic toxicity in older adults treated with gemcitabine or a gemcitabine-containing regimen in routine clinical practice: a multicenter retrospective cohort study.

Older adults receiving cytotoxic agents may be more susceptible to hematologic toxicities because of progressive reduction in organ functions and multiple co-morbidities. Because older adults are under-represented in clinical trials, this retrospective study aims to evaluate hematologic toxicity of gemcitabine-based regimens in older patients compared with their younger counterparts in clinical practice. A total of 494 patients routinely treated with gemcitabine, either alone or in combination with platinum-based drugs, in the Slotervaart Hospital or The Netherlands Cancer Institute between January 2003 and January 2013 were enrolled. Patient characteristics, underlying malignancy, treatment regimen, administered doses of gemcitabine, and laboratory values were retrospectively collected from electronic patient records. The relative dose intensity achieved in older patients and their younger counterparts was evaluated using the Wilcoxon rank sum test. Incidence of hematologic toxicity in older adults (age ≥70 years) and their younger counterparts (age <70 years) was compared using the Fisher's exact test. Predictors of experiencing Grade 3 or 4 hematologic toxicity were evaluated using logistic regression. Patient characteristics and baseline laboratory values were equally distributed among the two age groups, except for the estimated glomerular filtration rate being significantly lower in the older patients. Reduction of the first administered dose of gemcitabine was significantly more frequently applied in the older patients (p = 0.03). However, no significant difference in the gemcitabine relative dose intensity over the median number of four treatment cycles was observed (65 % in the older patients group vs. 67 % in the younger control group). Incidence of severe hematologic toxicity (Grade ≥3) was not significantly higher in the older patients. A subset analysis of nadir blood counts showed a trend towards an increased incidence of Grade ≥3 hematologic toxicity for the older patients in the gemcitabine-cisplatin treatment group. Moreover, the relative risk for developing Grade 3 or 4 leukocytopenia in the older patients was increased fivefold (p = 0.007) for combination therapy with gemcitabine and cisplatin. Blood transfusions were administered nearly twofold more frequently in the older patients, but this difference did not reach statistical significance. Treatment with gemcitabine or a gemcitabine-containing regimen appeared to be feasible and well tolerated in the older patients who were selected to receive chemotherapy. Overall, patients ≥70 years of age did not incur a higher incidence of severe or life-threatening hematologic toxicity nor did they undergo more frequent or larger dose adjustments. These data support additional treatment-specific prospective studies and clinical trials in older cancer patients to optimize treatment benefit and risk in this heterogeneous older patient population.

Dismal outcome of T-cell lymphoma patients failing first-line treatment: results of a population-based study from the Modena Cancer Registry.

We conducted a population-based study to establish the outcome of T-cell lymphoma (TCL) patients failing systemic first-line therapy. All TCL patients failing first-line systemic therapy in the province of Modena were identified from Modena Cancer Registry between 1997 and 2010. A total of 53 patients were analysed. Regarding the type of failure, 18 patients relapsed, and 35 progressed during first treatment. Among relapsed patients, the median time from date of response to relapse after first treatment was 6.2 months (range 1.87-102). A total of 18 patients (34%) died before receiving salvage treatment, 21 received platinum or gemcitabine-containing regimens (7 addressed to autologous stem cell transplant (ASCT)), 12 other CT regimens; 2 received radiotherapy (RT). The median survival after relapse (SAR) was 2.5 months. After a median follow-up for living patients after failure of 35 months (range 8-111 months), 44 patients died, and the cause of death was found to be lymphoma progression in all (98%) but one of them. The median SAR was 2.5 months. The 3-year SAR was 19%. Univariate and multivariate Cox regression analyses for SAR were performed. In multivariate analysis, performance status and type of failure were associated with a higher risk of death after relapse. The outcome of TCL patients failing first-line therapy is poor. Only a few cases that could receive ASCT had promising chances of long remission. There is urgent need for novel agents for patients requiring second-line treatment.

The prognostic role of time to diagnosis and presenting symptoms in patients with pancreatic cancer

Background: The aim of this study was to investigate the prognostic role of diagnostic delay and clinical presentation (regarding pain, jaundice, and weight loss) in pancreatic carcinoma. Methods: One hundred and seventy patients with pancreatic cancer were diagnosed and treated in the decade 2001–2010 (100 males and 70 females, with a mean age of 65.8 years [range, 36–91]). Patients were staged with spiral computed tomography and 75% were found to have advanced disease (28 stage III, 99 stage IV disease). Ductal adenocarcinoma was diagnosed in 147 cases, other subtypes of carcinoma in the remaining 23. Fifty patients were operated with radical intent, 19 had palliative surgery, 101 were considered inoperable because of advanced disease or heavy anesthesiologic risk; 31 of these inoperable patients underwent biliary decompression by insertion of an endoluminal or percutaneous stent. Gemcitabine-containing regimens were administered to 143 patients and radiotherapy was combined in 19. Overall and relative survival were the parameters studied. Multivariate analysis was performed by multiple regressions applied to proportional-hazards model. Results: From all the clinical, pathological and therapeutical factors evaluated the statistically significant ones were time to diagnosis and surgery. Among symptoms pain was related to the shortest mean time to diagnosis, weight loss to the longest, with corresponding differences in survival. These differences of observed survival were substantially confirmed in terms of relative survival. Conclusions: The poor prognosis of pancreatic carcinoma seems to depend, in part, on diagnostic delay and this, in turn, is influenced by the type of presenting symptoms.