scholarly journals “IDENTIFYING HIGH-RISK CHRONIC LYMPHOCYTIC LEUKEMIA: A PATHOGENESIS-ORIENTED APPRAISAL OF PROGNOSTIC AND PREDICTIVE FACTORS IN PATIENTS TREATED WITH CHEMOTHERAPY WITH OR WITHOUT IMMUNOTHERAPY.”

2016 ◽  
Vol 8 ◽  
pp. 2016047 ◽  
Author(s):  
Sara Martinelli ◽  
Antonio Cuneo ◽  
Gian Matteo Rigolin
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Poor Performance ◽  
High Serum ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Poor Performance Status

 Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment is important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS), response to treatment and transformation into Richter’s syndrome (RS). We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our stringent criteria no parameter was found to independently predict for inferior response to treatment or development of RS.  

scholarly journals Low Intensity Alternative Induction Therapy for Acute Myeloid Leukemia (AML). Real World Experience from Tawam Hospital, United Arab Emirates

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4409-4409
Author(s):  
Arif Alam ◽  
Khaled al Qawasmeh ◽  
Philip L. McCarthy
Keyword(s):  
Older Adults ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Performance Status ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Response To Treatment ◽  
Poor Performance Status ◽  
Advisory Committees ◽  
Molecular Abnormalities

Abstract Introduction: AML is a heterogenous group of hematological neoplasms with morphological, cytogenetic and molecular abnormalities resulting in maturation arrest of myeloid cell lines. This translates into clinical symptoms and signs resulting from neutropenia, anemia and thrombocytopenia. Although the knowledge of the underlying biology and molecular abnormalities has evolved tremendously, this has not been accompanied as quickly by translational changes in the early management of AML patients. The intensive induction therapy (combination of anthracycline and cytarabine) for young patients with good performance status has remained static since the first description in 1973 (Yates et al, Cancer Chemother Rep. 1973; 57(4):485-8). Older adults and patients with comorbidities had inferior treatment choices limited to hypomethylating (HMA) agents. The activity of Venetoclax R (Ven) with either HMA or Low dose Cytarabine (LDAC) has improved the outcome of patients who are not candidates for intensive induction therapy. In this report we describe our experience with HMA alone or the combination of HMA and Ven in patients not fit for intensive induction therapy in a real-world setting. Method: We conducted a retrospective chart review of AML patients diagnosed between January 2020 and July 2021. Data collected included patient demographics, karyotype, treatment and response to treatment. Older adults were defined as patients greater than 60 years of age. Patients with comorbidities (renal failure, active cardiac, pulmonary and hepatic disease) active opportunistic infections and poor performance status (ECOG >2) were also deemed not suitable for intensive induction therapy. Results: Alternative induction was given with HMA (5 Azacitidine) alone or in combination with Ven. HMA dose (75mg/m 2 was calculated over a period of 7 days and given during workdays of the week. Ven was given 100 mg (with CYP3A4 inhibitor) - 400 mg per day for 21 days. Patients were evaluated for treatment response after 2 - 4 cycles. Between January 2019 and June 2021, 66 patients were diagnosed with AML. The median age was 45 years (range 16-95years). Older adults (>60 years of age) have increased from < 10 % to 28 % (n=19) in the current cohort (Alam A et al Blood 2014; 124 (21). Treatment was as follows: Intensive induction n= 29, alternative induction n=19 and no therapy n=18 (refused treatment, age and poor performance status). The median age of patients given alternative induction was 55 years (range 26-80 years). Karyotype analysis showed good risk n=3, intermediate risk n= 9 poor risk n=3, metaphase failure n=4. Alternative induction reasons included age (n=9), co-morbidities (n=10) (Obesity, respiratory failure, cardiomyopathy, pulmonary embolism, renal failure, acute hepatitis, active infection (mucormycosis) and 2ndry AML). The response to HMA and Ven consisted of CR 60 % (9/15) with 4 patients ineligible for evaluation (2 early death (day + 3 and day + 8), the other 2 < 28 days post induction). The progression free survival is 149 days (range 41-517 days). 3 patients have relapsed after achieving complete remission. The median overall survival (OS) for the cohort is 120 days (range 3 to 517 days) while the median OS for non-responders is 103 days (range 3 to 375 days). Conclusion: The combination of HMA and Ven is an effective treatment modality in newly diagnosed patients with AML who are not eligible for intensive induction. The response to treatment has improved from < 10 % (HMA alone) to 60 % with HMA + Ven in an older cohort or those with comorbidities. The treatment is given in outpatient setting with increased patient satisfaction and minimal toxicities. However, this is complicated by increasing issues with access due to insurance coverage and co pay for Ven. Standardization of HMA and Ven with or without CYP3A4 inhibitors may improve the CR rates. Consolidation strategies in younger patients (especially good risk disease) who are other wise ineligible for intensive induction may improve progression free survival. Disclosures McCarthy: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Juno: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Risk Factors for Overall Survival in Children with High Risk Acute Myeloid Leukemia (HR AML) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity of Conditioning Regimens

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Elena Vladimirovna Semenova ◽  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Hematopoietic Stem ◽  
Factors Influencing ◽  
Remission Status ◽  
Conditioning Regimens ◽  
The Moment

Background: Traditionally, children with AML undergo аllo-HSCT with myeloablative conditioning (MAC). It is known that MAC is associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities. But there is no conclusive evidence to support efficacy of RIC allo-HSCT in children suffering from different malignant diseases including AML. The aim: To compare efficacy of different intensity conditioning regimens in children with high risk (HR) AML (according to AML-BFM protocols 1998 and 2004) and to identify factors which have a prognostic significance for overall survival (OS). Patients and methods: Retrospective analysis was performed in 192 patients (pts) with AML (median age of 10 years (0.5-18 y.o.), who received allo-HSCT at R.M. Gorbacheva Research Institute between 08/2000 and 09/2019. MAC (busulfan- or treosulfan-based) were used in 109 pts: 1st CR - 46 pts (MRD+ n=11), 2nd CR - 18 pts, 3rd CR - 1 pt, relapse - 44 pts. Allo-HSCT with RIC were performed in 83 pts: 1st CR - 32 pts (MRD+ n=13), 2nd CR -19 pts, 3rd CR - 4 pts, relapse -28 pts (p=0,674). RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Indication for RIC allo-HSCT was poor performance status (Lansky/Karnofsky score ≤70%), or organ dysfunction due to previous therapy, or infectious complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 30 pts (16%), from matched unrelated donor - in 98 pts (51%), haploidentical - in 64 pts (33%) and the donor distribution was not different between groups (p=0,878). Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (53%). OS were estimated using Kaplan-Meier curves. Univariate analyses were performed using the log rank test for OS, Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment >=0,5x109/l was D+16 (range D+8-52). Engraftment was observed in 67 pts (81%) after RIC and 94 pts (86%) after MAC (p=0,231). OS after RIC allo-HSCT in the 1st CR was 76% and after MAC - 68% (p=0,014), in 2nd CR 50% after RIC and 54% after MAC (p=0,058), in advanced disease 14% after RIC and 16% after MAC (p=0,394). The transplant-related mortality rate was 19% after RIC and 22% after MAC (p=0,546). Risk of relapse was 28% after RIC and 26% after MAC (p=0,456). Factors influencing OS after MAC were: 1) Remission status at the moment of allo-HSCT (р=0.001); 2) Presence of aGVHD grade I-II (р=0,005); 3) Relapse or MRD+ status after allo-HSCT (р=0.012); 4) Lansky score >70% (р=0,024). Factors influencing OS after RIC were: 1) Remission status at the moment of allo-HSCT (1st remission) (p=0,001); 2) Lansky score >70% (р=0,004). Conclusion: The effectiveness of RIC and MAC is comparable in children with HR AML, but RIC demonstrated better results in 1st CR. The presence of I-II grade aGVHD had positive effect in MAC. Factors influencing OS in both groups were disease status at the moment of allo-HSCT and performance status before allo-HSCT The use of RIC can be effective in patients, especially those who have undergone allo-HSCT in the 1st remission, while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Multicenter studies are warranted, especially for patients in the first CR, where long-term complications are of most importance. Disclosures No relevant conflicts of interest to declare.

scholarly journals Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Weekly Schedule ◽  
Dose Reductions

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.

scholarly journals A Review of Docetaxel: Its Use in the Treatment of Gastric Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S5191
Author(s):  
Alessandro Inno ◽  
Michele Basso ◽  
Alessandra Cassano ◽  
Carlo Barone
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Phase Ii Studies ◽  
Combination Regimens

Docetaxel, a member of the taxane family, promotes cell death by binding β-tubulin and has demonstrated activity against several human malignancies, both as a single agent and in combination therapy. It has been approved in Europe and the US as front-line treatment for advanced gastric cancer in combination with cisplatin and fluorouracil (DCF regimen). This approval was based on the results of a pivotal study (V325) which demonstrated that the addition of docetaxel to the reference regimen of cisplatin and fluorouracil improves overall survival and progression-free survival with a better quality of life despite increased toxicity (mainly haematological). Modifications of DCF regimen have been successfully investigated as a means of making the treatment more tolerable and suitable also for elderly patients or patients with poor performance status. Emerging data from several phase II studies suggest that other docetaxel-based combination regimens with anthracyclines or irinotecan have interesting activity with acceptable toxicity profiles, but the true efficacy of these regimens needs to be assessed in large randomized phase III studies. Thus, the best docetaxel-containing regimen has yet to be identified. Docetaxel also represents a good candidate for combination with novel molecular target agents. In light of the high response rates observed in phase II-III studies, a docetaxel-based chemotherapy regimen might also be considered a treatment option as perioperative or adjuvant therapy in potentially curable gastric cancer and further studies with or without biological agents are eagerly awaited in this setting.

Phase II Study of Gemtuzumab Ozogamycin (GO) and Cytarabine (ARA-C) in Patients with High Risk MDS and AML..

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4723-4723
Author(s):  
Peter Kang ◽  
Karen Seiter ◽  
Delong Liu ◽  
Muhammad Arshad ◽  
Anila Qureshi ◽  
...  
Keyword(s):  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Complete Response ◽  
Lung Damage ◽  
Poor Performance Status ◽  
High Cumulative Dose ◽  
History Of ◽  
M 12 ◽  
To Receive

Abstract To evaluate the efficacy of GO + ara-c in high risk pts, we treated 22 pts with MDS (10) and AML (12) with cytarabine 100 mg/m2/d x 7 d and GO 9 mg/m2 x 1 on d 4. Pts with MDS were eligible if they had [1] RAEB-1 and either hgb < 8 gm/dl, platelet < 50,000/mm3, neutrophils < 1000/mm3, or cytogenetics other than 5q-, 20q-, -y, or normal, [2] RAEB-2, or [3] CMML. Pts with AML (newly diagnosed or relapsed) were eligible if they were ineligible for anthracycline-based therapy (poor performance status: 2 pts; low ejection fraction or high cumulative dose of anthracyclines: 6 pts, both reasons: 4 pts). The median age was 66, M:12, F:10. Diagnoses: RAEB-1: 4, RAEB-2: 5, CMML: 1, AML, newly dx’d: 7, AML relapsed: 5. Cytogenetics were high risk: 10, intermediate risk: 11 pts, low risk: 1 pt. Overall, 18% had a complete response (CR) after one cycle of therapy. Three pts (14%) had a partial response (PR), of which one had a CR after a second course of therapy. Of the pts with AML: CR: 2/12, PR: 2/12, Failure (F): 5/12, Toxic Death (TD): 3/12. For pts with MDS: CR: 2/10, PR: 1/10, F: 5/10, TD: 2/10. Toxicities included neutropenic fever/sepsis, mucositis, diarrhea, increased LFTs, hemorrhage. One pt with a history of ABVD and RT to chest for HD developed direct pulmonary toxicity due to chemotherapy (diffuse pulmonary infiltrates, biopsy proven toxic lung damage). Although overall response rate is modest, some pts had remarkable responses: One pt with RAEB-1, transfusion dependent and multiple high risk cytogenetics (−5, −7, multiple others) remains in CR (including cytogenetic CR) 7 months post treatment. A second pt with RAEB-1, transfusion dependent and multiple high risk cytogenetics (−5, −7, multiple others) had a PR after one course, but was unable to receive further chemotherapy due to toxicity. The latter pts suggest that this regimen should be studied further in pts with MDS, poor risk cytogenetics and low blast counts.

Combination Chemoimmunotherapy with Pentostatin, Cyclophosphamide and Rituximab Shows Significant Clinical Activity with Low Accompanying Toxicity in Previously Untreated B-Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 35-35
Author(s):  
Neil Kay ◽  
Susan Geyer ◽  
Timothy Call ◽  
Tait Shanafelt ◽  
Clive Zent ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Significant Clinical Activity

Abstract BACKGROUND: B-Chronic Lymphocytic Leukemia (CLL) is still uncurable but very powerful new tools are available with the use of chemoimmunotherapy (CIT). Purine nucleoside-based regimens that incorporate rituximab have generated very high levels of overall responses (OR) with significant percentage of those complete responses (CR) in previously untreated CLL. Here we report and update our experience with a phase 2 pentostatin-based CIT regimen for previously untreated CLL as conducted at 2 medical centers. We also studied the association of outcome based on risk stratification parameters and achievement of minimal residual disease. METHODS: Building on prior work of pentostatin in CLL by us (Kay ASH, 2004) and others, we initiated a trial of combined pentostatin (P)(2 mg/m2), cyclophosphamide (C)(600 mg/m2) and rituximab (R)(375 mg/m2) for symptomatic, previously untreated patients (n=65). This PCR regimen is given on a 21-day, 6-cycle schedule. However, the initial cycle of treatment uses thrice weekly rituximab as described by us earlier. In brief, this was rituximab at 100 mg/m2 on day 1, 375 mg/m2 on days 3 and 5 of the first week only. Prophylactic Sulfamethoxazole/Trimethoprim and Acyclovir were given to all patients for 1 year starting on the first cycle of therapy with PCR. All patients were risk stratified using CD38, ZAP-70, immunoglobulin heavy chain variable region gene (IgVH) and FISH panel assessments at entry. RESULTS: These patients were characterized as mostly in high-risk categories. Of 64 evaluable patients, 34 (53%) were high Rai risk (stage 3–4), 71% were non mutated for the IgVH gene, 34% were CD38+ and 34% were ZAP-70+. Thirty patients (52%) had one FISH anomaly, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs, and no major infections. NCI Working Group Criteria Responses occurred in 58 (91%) with 26 (41%) complete responses (CR), 14 (22%) nodular partial responses (nodular PR), and 18 (28%) partial responses (PR) patients. Outcome for all 64 patients demonstrates a median progression-free survival of 32.6 months. Importantly, no high risk factor (i.e., age, FISH, IgVH status, CD38+, ZAP-70+) except for del (17p) defect (n=3) precluded attaining a CR or NPR. In contrast, we found this regimen was equally effective in young vs. elderly (>70 yrs) patients and in del(11)(q22.3) vs. other favorable prognostic FISH factors. Examination of outcome among CR and nodular PR patients for PFS by flow cytometry status (negative vs. positive, i.e., ≤ 1 % CD5+/CD19+ vs. ≥ 1 % CD5+/CD19+) demonstrated improvement in progression free survival for patients who attained flow cytometry negativity (p = 0.009). Conclusion: This novel regimen of pentostatin, cyclophosphamide and rituximab for previously untreated CLL demonstrated significant clinical activity despite poor risk-based prognoses with minimal toxicity in terms of bone marrow suppression and/or infections. The additional feature of this approach is the ability to have durable responses for all age groups and even CLL patients with a del(11)(q22.3).

Should all patients (pts) with advanced biliary cancers receive first-line treatment with cisplatin and gemcitabine (GC)?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 244-244
Author(s):  
Vanessa Costa Miranda ◽  
Luiza Dib-Faria ◽  
Maria Ignez Freitas Melro Braghiroli ◽  
Jorge Sabbaga ◽  
Daniel Fernandes Saragiotto ◽  
...  
Keyword(s):  
Median Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Poor Performance ◽  
Median Number ◽  
Poor Performance Status ◽  
Poor Survival ◽  
First Line ◽  
Dismal Prognosis

244 Background: GC is considered the standard of care for pts with advanced biliary tract cancer (BTC), providing median survival of nearly one year. (Valle J et al. NEJM 2010) Nevertheless, many pts experience poor outcomes, leading to a growing interest to identify pts who might benefit from such treatment. Here we aimed to investigate clinical and laboratory factors associated with poor survival among BTC pts treated with GC. Methods: We retrospectively evaluated all consecutive pts with advanced/metastatic BTC who received first line GC at the Instituto do Cancer do Estado de Sao Paulo, Brazil, in a 2 year-period. Clinical and laboratory variables that could influence pts’ outcomes were gathered from medical charts. Cox regression proportional hazard model was used to investigate the following prognostic factors for death: pre-treatment biliary deobstruction, baseline Ca 19.9, any GC interruptions or dose reductions, baseline ECOG status, Charlson Comorbidity Index (CCI) and age. P values < 0.05 in multivariable analysis were considered significant. Results: From January/2009 to July/2011, 72 pts were identified. The median age was 60 years (range 30-80 years), 45 pts (62.5%) were female and 50 (69.4%) presented baseline ECOG 0-1. The median number of cycles of CG was 4 (range 1-9). Grade 3 /4 neutropenia and thrombocytopenia occurred in 16.6% and 12.5% of pts, respectively. Median survival of the whole cohort was 9.53 months (95% CI: 6.2 - 11.4). Median survival in pts with ECOG 0/1 was 13.5 months (95% CI: 9,5 – NR) and among pts with ECOG 2/3 3,5 months (95% CI: 1-7). In the Cox multivariable model, ECOG 2 /3 versus 0/1 (HR: 8.4, 95% CI: 3.4 to 20.7; p<0.001) and CCI score ≥ 2 (HR: 9.5 95% CI: 1.6 to 55.3; p= 0.012) significantly predicted for poor survival. There was a trend for improved survival among pts who had biliary drainage before starting GC (HR: 2.3 95% CI: 1.0 - 5.3; p= 0.051). Conclusions: In this retrospective cohort of unselected pts with advanced BTC treated with first line GC, poor performance status and multiple comorbid illnesses were associated with dismal prognosis. Treatment with GC should be carefully discussed before being offered to these pts.

Current and Emerging Treatments for Metastatic Renal Cell Carcinoma

2018 ◽  
Vol 18 (5) ◽  
pp. 468-479 ◽  
Author(s):  
Carla Cavaliere ◽  
Carmine D`Aniello ◽  
Chiara Della Pepa ◽  
Salvatore Pisconti ◽  
Massimiliano Berretta ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Special Focus ◽  
Systemic Treatments

In the last decades, the treatment of mRCC, metastatic Renal Cell Carcinoma, has become more and more complex due to the approval of a great number of effective systemic treatments that have significantly improved the prognosis of patients suffering from such disease. An additional knowledge of the genetic aberrations and the molecular pathways alterations that underlie RCC, has promoted the development of several novel agents, known as target therapies (TTs). Even though TTs are not curative and all patients eventually progress, an adequate sequencing of these drugs can provide a significant benefit in terms of PFS, Progression Free Survival, and hopefully OS, Overall Survival. To date, there are few data about the optimal sequential use of the TTs hence, in clinical practice, the therapeutic strategy is chosen on the basis of the safety profile of the drug, patients medical history and the pivotal trial results, though such studies often exclude patients with poor performance status and/or severe comorbidities that we routinely see in our clinics. This review aims to provide an overview of the systemic therapies for mRCC both in the newly diagnosed patients and in the subsequent lines of treatment, with a special focus on the last advances about TTs and immunotherapy.

Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged > 65 years with advanced pancreatic cancer (APC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 705-705
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  
Keyword(s):  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Weekly Schedule ◽  
Free Survival ◽  
Kaplan Meier ◽  
Ecog Ps ◽  
Dose Reductions

705 Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in APC. However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients > 65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged > 65 years with chemo-naive APC and ECOG PS < 2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using Kaplan-Meier method. Adverse events were recorded on the day of chemotherapy. CA19-9 was measured every cycle and restaging scans were performed every two cycles. Results: Seventy-three patients (median age: 73; range: 66 - 93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months respectively. 66% of patients received growth factor support based on ASCO guidelines and no patients developed neutropenic fever. The incidence of grade > 3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5% respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients respectively. Conclusions: In patients > 65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with historical control from the MPACT study. This regimen allowed for less dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as favorable side effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with APC and poor performance status. Better tolerability may allow for combination with a third agent, such as a targeted or immunotherapy.

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