Clinical and molecular determinants of survival in pancreatic cancer patients treated with second line chemotherapy: results of an Italian/Swiss multicenter survey

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4622-4622 ◽  
Author(s):  
A. Mancuso ◽  
S. Sacchetta ◽  
P. Saletti ◽  
C. Tronconi ◽  
L. Milesi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Stable Disease ◽  
Rank Test ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Log Rank Test ◽  
Line Therapy ◽  
Line Chemotherapy

4622 Background: The impact on survival of palliative second-line therapy in pancreatic cancer has not been clarified and clinical/molecular predictive factors are needed in order to decide which therapeutic regimens may be effective. Methods: Clinical records of 160 Gemcitabine resistant/refractory pancreatic cancer patients (pts) treated in 11 medical oncology departments in Italy and Switzerland were reviewed. All pts received a second line regimen from June 1997 to February 2006. There were 99 males, 61 females, median age 62 years (range 34–78) and median ECOG performance status (PS): 1 (range 0–2). 16 different salvage regimens were administered consisting of monotherapy with fluoropyrimidines in 59% of cases and combinations of platinum- salts/fluoropyrimidines in 36%. Fluoropyrimidines combinations with bevacizumab, irinotecan and mitomycin C were administered in the remaining 5%. ERCC-1 expression was examined by performing immunohistochemical staining in pts treated with platinum-salts. Results: Second line chemotherapy produced partial responses (PR) in 16 (10%) and stable disease (SD) in 40 pts (25%) by RECIST criteria. The median progression free survival (PFS) was 2.65 months. Multivariate analysis revealed that the most important prognostic factor for PFS was PS at the beginning of second line therapy (Second line PFS PS=0–1 vs PS=2: 78 days vs 48 days, p<0.05, log-rank test). Pts who had responded (PR) to first-line Gemcitabine were more likely to respond or attain stable disease after second-line treatment, with a PFS of 2.6 vs 1.6 months (p<0.05, log-rank test). The overall survival (OS) for all evaluable pts was 11.5 months and 1-year survival was 45%. Among 57 pts treated with platinum-containing doublets, a low ERCC1 level (28/57 pts) was highly predictive of longer survival (11.9 versus 9.9 months, p<0.05 log-rank test). Conclusions: These results suggest that fluoropyrimidine-based salvage regimens have marginal activity and should be considered only in pts with a good PS who have responded to first line chemotherapy. ERCC-1 expression should be further evaluated as a predictive test to select patients who may benefit from platinum/fluoropyrimidine salvage regimens. No significant financial relationships to disclose.

Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14107-14107
Author(s):  
A. Mancuso ◽  
P. Saletti ◽  
S. Sacchetta ◽  
E. Romagnani ◽  
F. Cavalli ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Stable Disease ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Second Line Chemotherapy ◽  
Line Therapy ◽  
Clinical Records ◽  
Line Chemotherapy

14107 Background: Recent advances in the treatment of pancreatic cancer might influence the management of locally advanced and metastatic disease, nonetheless prognosis remains dismal (1-year survival rates: 24%). The impact on survival of palliative second-line therapy is hotly debated. Methods: We retrospectively reviewed the clinical records of 103 pancreatic cancer patients admitted to San Camillo/Forlanini Hospital (Rome, Italy) and the Oncology Institute of Southern Switzerland during the period June, 1997 to August, 2005 [60 males, 43 females, median age 65 years (range 43–80); median ECOG performance status (PS): 1]. All patients received Gemcitabine as single agent (90%) or in combination with Oxaliplatin (10%) as upfront therapy. A total of 12 fluoropyrimidine-based salvage regimens were administered to 46 patients in the second line setting. Best supportive care was selected in 57 patients after failing first line therapy. Results: Of 103 evaluable patients, first line chemotherapy produced overall tumor growth control of partial response (PR) and stable disease(SD) by RECIST criteria of 52.4% with a median progression free survival (PFS) of 4.6 months. Multivariate analysis revealed that the most important prognostic factor for PFS was the patient’s PS, as patients with PS of 1–2 at diagnosis had significantly worse results than patients with PS = 0 (First line PFS: 110 days vs 193 days, p<0.05). Baseline CA19–9 and number of metastatic sites were not independent prognostic factors for better first-line PFS. PR was observed in 8/46 patients (17.3%) who received second line chemotherapy, SD in 10 (21.7%), and 28 patients progressed (61%). Median overall second line PFS was 3.2 months. Patients who had responded to first-line Gemcitabine were more likely to respond or attain stable disease with second-line treatment, with a PFS of 5.6 vs 2.85 months (p<0.05). The overall survival for all evaluable patients was 8.4 months. 1-year survival was 52% for patients treated with second line therapy. Conclusions: These results are consistent with historical studies and suggest that fluoropyrimidine-based salvage regimens have marginal but definite activity and should be considered in patients who have responded to first line chemotherapy with an optimal PS. No significant financial relationships to disclose.

scholarly journals Multicenter Retrospective Analysis of Second-Line Therapy after Gemcitabine Plus Nab-Paclitaxel in Advanced Pancreatic Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1131 ◽  
Author(s):  
Valeria Merz ◽  
Alessandro Cavaliere ◽  
Carlo Messina ◽  
Massimiliano Salati ◽  
Camilla Zecchetto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
Second Line ◽  
Second Line Therapy ◽  
Clear Trend ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Number Of Patients

Pancreatic cancer is one of the most lethal solid tumors. In many European countries gemcitabine plus nab-paclitaxel is the preferred first-line treatment. An increasing number of patients are eligible for second-line therapy, but the best regimen is still controversial. This study aimed to evaluate the efficacy of oxaliplatin-based compared to irinotecan-based therapies in this setting. 181 advanced pancreatic cancer patients consecutively treated in three centers with a second-line therapy progressed on gemcitabine plus nab-paclitaxel were retrospectively enrolled. OS and PFS were calculated using the Kaplan-Meier method and survival of the two groups was compared using the log-rank test. The median PFS and OS were respectively 3.5 (95%CI 3.2–3.8) and 8.8 months (95%CI 7.9–9.8) from second-line therapy in the overall population. The median PFS and OS were respectively 3.3 (95%CI 3.1–3.5) and 8.2 months (95%CI 7.24–9.34) with an irinotecan-based combination compared to 4.0 (95%CI 2.4–5.7) and 10.3 months (95%CI 8.62–12.02) in patients receiving an oxaliplatin-based combination. We observed a clear trend for longer survival outcomes with platinum-based doublet compared to regimens including irinotecan or nal-IRI. Head-to-head trials are still lacking. The neutrophil-to-lymphocyte ratio and the presence of liver metastases could drive physicians in tailoring the treatment strategy.

Efficacy of Cyclosporine Treatment in Patients with MDS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4608-4608
Author(s):  
Alina Kokhno ◽  
Elena Parovitchnikova ◽  
Elena Mikhailova ◽  
Yulia Olshanskaya ◽  
Irina Kaplanskaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stable Disease ◽  
Response Rate ◽  
Bone Marrow Failure ◽  
Normal Karyotype ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Myelodysplastic syndrome (MDS) represents a heterogenous group of myeloid neoplasms characterized by abnormal differentiation and maturation of myeloid cells, bone marrow failure and genetic instability. The recent clinical and laboratory investigations suggest that MDS is closely related to diseases in which the bone marrow failure is mediated at least in part by the immune system. The are few studies concerning the of efficacy of treatment of MDS pts with cyclosporine A (CSA) but they are limited to the group of pts with bone marrow hypoplasia. The aim of our study was to evaluate the efficacy of CSA treatment in MDS pts as first line or second line therapy. 48 pts with different forms of MDS were included in study. The group of first line CSA treatment included 30 pts, male-18/female-12, RA-3, RARS-1, RCMD-18, RAEB-7, RAEBt-1, 20-normal karyotype, 10-different abberations including: 5q−, 16q+, −7, 12q+, −Y, [11p+,7q−] and complex abb. Hypoplastic bone marrow was revealed in 15 pts, hyperplastic-8 pts, hypo/hyper-7 pts. Second line therapy group included 18 pts, male-9/female-9, RCMD-11, RARS-1, RAEB-5, RAEBt-1, normal karyotype-3, cytogenetic anomalies-13 (+8, 5q−,−7, +8 and complex abb.). Hypoplastic bone marrow was revealed in 12 pts, hyperplastic-4 pts, hypo/hyper-4 pts. The first line therapy consited of splenectomy in 8 pts, low doses of Ara-C-3, interferon-α-3, chemotherapy-2 and ATG-2 pts. CSA was applied at 5–10 mg/kg/day initially and then adjusted according to blood levels and toxicity. The maintenance dose was 1–3 mg/kg/day. Minimum time to response evaluation was one month. Complete response (CR) was defined as normal PB counts, BM aspirate; partial response-improvement of PB counts to 50% of normal and freedom from transfusions; stabilization-decrease of transfusion requirements and stabilization of PB counts for more then 1 month. Total response rate in first group was 60% (18 pts) with median follow up of 10 months (2–134). CR was estimated in 20% (6pts), median follow-up 72 months (44–134). 2 pts with CR are in clonal remission. 2 pts from response group developed acute leukemia (AL). 40% of pts showed no response.58% of pts without response developed RAEB or AL. 42% of pts were in stable disease and were treated with another modalities. The response rate in second group was 61% (11 pts) with median follow-up of 7 months (1–78). 22% (4 pts) achieved CR, median follow-up 60 months (43–78). 39% of pts showed no response. 71% from these pts (5) transformed to RAEB or AL. 2 pts remained in stable disease. In both groups response was registrated from 1 to 4 months from treatment initiation (median 3 months). CR was achieved in the majority of pts after 1 year of treatment. Response was achieved in 77% of pts with hypo/hyper and hypoplastic bone marrow and in 12% of pts with hyperplastic bone marrow. Overall survival was decreased in pts with more the 5% blasts in bone marrow (p=0,02 for 1st line group, p=0,075 for 2nd line group), and increased for pts with hypo and hypo/hyper bone marrow cellularity (p=0,002 for 1st line group). There was no impact of cytogenetics. We may conclude, that CSA demonstrates good efficacy in therapy of MDS pts, especially for pts with RA, RARS and RCMD with hypo and hypo/hypercellular bone marrow and reactive lymphoid nodules in bone marrow. It can be initiated as 1st or 2nd line therapy and should be continued at least for 3 months before evaluating of response.

Role of Rituximab and Intensification with Autologous Stem Cell Transplantation in Primary Mediastinal B-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4851-4851
Author(s):  
Vittorio Ruggero Zilioli ◽  
Chiara Rusconi ◽  
Cristina Gabutti ◽  
Giovanni Grillo ◽  
Elisa Zucchetti ◽  
...  
Keyword(s):  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Progressive Disease ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Fdg Uptake ◽  
Line Therapy ◽  
Line Chemotherapy

Abstract Abstract 4851 Background: Primary Mediastinal B-Cell Lymphoma (PMBL) is an uncommon disease, characterized by aggressive and invasive course but with a good prognosis after anthracycline-based chemotherapy. In the PET era the role of consolidation radiotherapy is under debate and, despite CD20 expression, the efficacy of Rituximab is still unclear. We retrospectively analyzed the outcome of 36 consecutive patients (pts) affected by PMBL treated in the last 10 years at our institution. We focused on anti-CD20 antibody efficacy when added to chemotherapy and on the role of autologous stem cell transplantation (ASCT) in PET positive pts after first-line treatment. Patients and methods: From June 2000 to March 2011 36 pts with biopsy proven PMBL referred to our institution. Median age was 35 years (range: 18–68); 21 pts (58%) were female and a mediastinal bulk at diagnosis was documented in 33 pts (92%). B-symptoms were reported in 16 cases (44%) and an extra-nodal involvement in 19 cases (53%). Age-adjusted IPI score was ≥ 2 in 12 pts (33%). For all patients first line treatment consisted in a third generation anthracycline-based chemotherapy (VACOP-B), with the addiction of 6 Rituximab doses in 15 pts (42%). Pts obtaining complete remission (CR) with negative PET after (R)-VACOP-B were consolidated by radiotherapy (RT), while pts in partial remission (PR) with residual FDG uptake underwent a second-line chemotherapy with 3 DHAP cycles followed by autologous stem cell transplantation (ASCT). Results: In the whole cohort, after first-line therapy overall response rate (ORR) was 97%, with a CR rate of 39%. RT was therefore performed in 14 PET-negative pts. 2/14 pts experienced early relapse and only one of them obtained a second CR after salvage therapy, while the non-responding patient died because of progressive disease. Twenty-one pts (58%) showed a residual FDG uptake after (R)-VACOP-B and underwent second-line therapy. Nineteen pts responding to second-line therapy achieved ASCT, while 2 pts progressed and died after salvage therapy. ORR after ASCT was 86% with a CR rate of 71%. Post-ASCT RT was performed in 10 pts, 7 CR and 3 PR; two PR pts converted to CR after RT. With a median follow-up of 66 months (range: 13–142) 2-year overall survival (OS) and progression free survival (PFS) were respectively 94% and 89%. Among the 15 pts receiving first-line chemotherapy containing Rituximab, ORR after R-VACOP-B was 93% with a CR rate of 40%. RT was therefore performed in 6 PET-negative pts. 1/6 pts experienced early relapse and died of progressive disease. One patient showed progressive disease after R-VACOP-B and underwent second-line therapy with ASCT, obtaining CR. Eight pts (53%) showed a residual FDG-uptake after R-VACOP-B and underwent second-line therapy and ASCT. ORR and CR rate after ASCT were 100% and 75% respectively. Two pts in PR after ASCT converted to CR after RT. Among the 21 pts receiving chemotherapy without Rituximab, ORR after VACOP-B was 100% and CR rate was 38%. RT was therefore performed in 8 PET-negative pts; one of them experienced early relapse and obtained a second CR after salvage therapy. Thirteen pts (62%) showed a residual FDG-uptake after VACOP-B and underwent second-line therapy. Eleven pts responding to second-line therapy achieved ASCT, while 2 pts progressed and died after salvage therapy. ORR and CR rate after ASCT were 77% and 69% respectively. No statistically significant difference in ORR, CR rate, OS and PFS (Figure 1) was found between pts treated with Rituximab plus chemotherapy and pts treated with chemotherapy alone. Conclusions: These data substantially confirm the satisfactory outcome of PMBL, with a 2-year OS and PFS of 94% and 89% for the entire cohort. We registered a residual FDG uptake after first line chemotherapy in a proportion of pts higher than expected (58%). This subgroup of pts clearly take advantage from second line chemotherapy followed by ASCT, obtaining a CR rate of 71%. The addiction of Rituximab to first line chemotherapy instead does not seem to improve PMBL pts outcome in this small and retrospectively analyzed population. The role of immunotherapy in this rare lymphoma subtype and the chance to safely avoid RT consolidation in PET negative pts need to be further investigated in wider prospective trial. Disclosures: No relevant conflicts of interest to declare.

Pulsed high-dose erlotinib with gemcitabine as second-line therapy for pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 421-421
Author(s):  
Christopher Larson ◽  
Tony R. Reid
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Dose Escalation ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Recommended Phase Ii Dose

421 Background: The options for treatment of pancreatic cancer follow progression on first line therapy are limited and associated with significant toxicity. Erlotinib has been approved for treatment of pancreatic cancer in first-line therapy. We conducted a phase I dose-escalation trial of erlotinib in combination with gemcitabine for patients that had failed first-line therapy. Erlotinib was administered by a novel pulse-dose schedule where the drug was given orally for 3 days every two weeks. Purpose: Assess the safety and determine a recommended phase II dose for pulsed high dose erlotinib in combination with gemcitabine for pancreatic cancer, and obtain preliminary data on activity. Methods: Patients with pancreatic cancer that progressed on or after first-line therapy were treated in a dose escalation study with erlotinib at 750 to 2,000 mg daily for three days every two weeks in combination with weekly gemcitabine at 1,000 mg/m2 for three weeks on and one week off. Results: No dose limiting toxicities were encountered and erlotinib-induced rash was mild and transient. Median overall survival was 6.7 months and 12-month overall survival was 27%. Progression free survival but not overall survival was longer in patients who did not previously receive gemcitabine. Rash was not associated with longer survival. Conclusions: The recommended phase II dose is erlotinib 2,000 mg daily for three consecutive days every two weeks in combination with gemcitabine. Tolerability was excellent, and outcomes were better than expected for second-line therapy in pancreatic cancer. Further studies are warranted, both as therapy after first-line and as first-line therapy for patients unable to tolerate more aggressive regimens. Clinical trial information: NCT02154737.

Second-line therapy with pemetrexed after gemcitabine failure in patients with unresectable locally advanced or metastatic pancreatic cancer: A multicenter phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4124-4124 ◽  
Author(s):  
S. Boeck ◽  
K. Weigang-Koehler ◽  
M. Fuchs ◽  
E. Kettner ◽  
D. Quietzsch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Phase Ii ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

4124 Background: There is no established second-line therapy for advanced pancreatic cancer after failure of standard first-line treatment with gemcitabine. In view of the urgent need of such therapy and the observation of clinically meaningful responses with pemetrexed in previously untreated pancreatic cancer, this phase II study evaluated pemetrexed as second-line therapy. Methods: This study was planned to evaluate the efficacy and safety of pemetrexed in 54 patients (pts) with unresectable locally advanced or metastatic pancreatic cancer (stage II-IV), ECOG performance status ≤2 and estimated life expectancy of ≥12 weeks (wks) after failure of first-line gemcitabine single agent or combination therapy. Pemetrexed was started at 500 mg/m2 q3w (10 min infusion), with vitamin B12 and folic acid supplementation. Dose escalation by 100 mg/m2 every other cycle and an unlimited number of cycles were allowed. Primary endpoint was the 3-month survival rate. Results: A total of 189 treatment cycles (median 2, range 1–20) was given to 52 pts (60% male, median age 63 yrs, median time since initial diagnosis 32 wks, 89% stage IV disease). Doses were escalated in 2 pts (4%) and reduced due to toxicity in 9 pts (17%); median dose per cycle was 500 mg/m2 (range 212–700 mg/m2). The 3-month survival rate was 75% (95% CI 63.2–86.8%). At a median follow-up of 20 wks, the median overall survival estimate was 20 wks, with 9 pts alive including 1 still on pemetrexed. Median TTP was 7 wks (range 1–62 wks). The overall response rate was 3.8% (0 CR, 2 PR); 12 pts (23%) had SD for ≥6 wks, 9 of them for ≥12 wks. CA 19–9 decreased at least once by ≥ 50% in 12 pts (23%). Grade 3/4 hematological toxicity rates per pt were as follows: neutropenia 17.3% (febrile neutopenia: 3.8%), leukopenia 15.4%, thrombopenia 5.8% and anemia 3.8%. Conclusion: Pemetrexed is a feasible option for second-line therapy with mild toxicity and encouraging activity in unresectable locally advanced or metastatic pancreatic cancer after gemcitabine failure. [Table: see text]

Continued cetuximab in second-line treatment for patients with unresectable metastatic wild-type KRAS, NRAS, and BRAF colorectal cancer after disease progression during first-line cetuximab-based therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 127-127
Author(s):  
Ying Liu ◽  
Feng Wang ◽  
Ning Ma ◽  
Shuning Xu ◽  
Lei Qiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Second Line Chemotherapy ◽  
Line Therapy ◽  
Ecog Ps ◽  
Line Chemotherapy

127 Background: Cetuximab plus chemotherapy is a first-line treatment option for metastatic RAS wild type colorectal cancer patients. Currently, no data are available on continuing cetuximab or changing bevacizumab as second-line therapy beyond first-line cetuximab-based chemotherapy. Methods: Patients (aged ≥18 years) with metastatic, histologically and genetically confirmed wild-type KRAS, NRAS and BRAF colorectal cancer progressing after first-line cetuximab plus chemotherapy were randomly assigned (1:1 ratio) to second-line chemotherapy with cetuximab (arm A) or with bevacizumab (arm B) 2·5 mg/kg per week equivalently. The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The second endpoint was overall survival (OS). Results: 77 Patients (from July 1, 2016 to Sept 20, 2019, 77) were randomized (41 in arm A and 36 in arm B). ORR was 29.3% and 19.4% in Arm A and Arm B ( p= 0.31). PFS was 7.2 months (95% CI 5.2–9.2) for Arm A and 5.9 months (95% CI 5.1–6.7) for Arm B ( p= 0.677). OS was 18.5 months (95% CI 15.1–21.8) for Arm A and 17.5 months (95% CI 15.4–19·7) for Arm B ( p= 0.444). Patients with ECOG PS 0 had significantly longer PFS and OS than ECOG PS 1 in second-line therapy whether cetuximab or bevacizumab combined with chemotherapy. ECOG 0 group vs ECOG 1 group, PFS was 8.7 months vs 4.6 months (p = 0.00) and OS was 21.2 months vs 12.3 months (p = 0.00). Moreover, ETS may predict efficacy of second-line continued cetuximab. The most frequently grade 3–4 adverse events in both arms were neutropenia (19.4% VS 16.7%), diarrhea (7.5% vs 11.1%), and nausea(10% vs 13.9%). Conclusions: Continuing cetuximab or changing bevacizumab plus standard second-line chemotherapy in patients with metastatic wild-type KRAS, NRAS and BRAF colorectal cancer after first-line cetuximab plus chemotherapy have similar clinical benefits. ECOG score is an independent predictor of prognosis and second-line treatment efficacy for colorectal cancer.

Esophageal Cancer: A Critical Evaluation of Systemic Second-Line Therapy

2011 ◽  
Vol 29 (35) ◽  
pp. 4709-4714 ◽  
Author(s):  
Christiane Maria Rosina Thallinger ◽  
Markus Raderer ◽  
Michael Hejna
Keyword(s):  
Esophageal Cancer ◽  
Targeted Therapies ◽  
Single Agent ◽  
Critical Evaluation ◽  
Individual Therapy ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Line Chemotherapy

The objective of this article was to review clinical trials that used antineoplastic second-line chemotherapy and/or targeted therapies in patients with esophageal cancer after first-line therapy. Computerized (MEDLINE) and manual searches were performed to identify articles published on this topic between 1996 and 2011. Twenty-five published trials and four abstracts presented at scientific meetings were identified. A total of 10 trials included only patients with squamous cell carcinomas (SCCs), four focused exclusively on adenocarcinoma (AC), the remaining 15 studies included both SCC and AC. The majority of trials (17 of 29) used docetaxel in combination with platinum analogs, eight used single-agent cytotoxic chemotherapy, and six evaluated targeted therapies. The numbers of patients were relatively small, ranging from eight to 55 patients. The response rates were generally low (between 0% and 39%), with only two small studies reporting objective responses of 50% and 63%, respectively. Time to progression ranged from 1.4 to 6.2 months, and the overall survival was disappointing at 4.0 to 11.4 months. Approximately 40% of patients who experience progressive disease after first-line chemotherapy are able to undergo second-line treatment. On the basis of data published so far, no standard second-line therapy has emerged. Future research will need to focus on individual therapy strategies such as genetic receptor mutations to increase the therapeutic outcome.

Real-Life Comparison Of Severe Vascular Events and Other Non-Hematological Complications In CML Patients Treated With Second Line Nilotinib Or Dasatinib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1491-1491 ◽  
Author(s):  
Joanna Gora-Tybor ◽  
Ewa Medras ◽  
Malgorzata Calbecka ◽  
Agnieszka Kolkowska ◽  
Edyta Ponikowska-Szyba ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Real Life ◽  
Rank Test ◽  
Second Line ◽  
Vascular Events ◽  
Second Line Therapy ◽  
Advisory Committees ◽  
Log Rank Test ◽  
Line Therapy

Abstract Despite very good long-term results of imatinib (IM) in chronic myeloid leukemia (CML) patients about 30% of them will need the new treatment option. For these patients, two effective second-generation tyrosine kinase inhibitors (TKI) are available: dasatinib and nilotinib. Although both have good toxicity profile and side effects are usually mild and manageable, some patients have major problems and develop intolerance or even life-threatening adverse events (AEs). A unique spectrum of non-hematological AEs has been reported for both TKI like pleural infusion for dasatinib and elevation of glucose, pancreatic and liver enzymes for nilotinib. Recently several studies have described the clinical manifestation of peripheral artery occlusive disease (PAOD) in patients receiving nilotinib. The risk of developing PAOD on TKI therapy is unknown and causality has not been established yet. We retrospectively analyzed the rates of grade 2-5 non-hematologic AEs in CML patients treated with dasatinib or nilotinib as second line therapy in “real-life” setting. The analysis included 105 patients from 5 Polish Hematological Centers, 57 men (54%) and 48 women (46%), with median age of 57 (range 21-88). Median time of observation was 28 months (range 1-93 months). Fifty-five (52%) patients were treated with nilotinib and 50 (48%) with dasatinib. The reason for stopping first line therapy was resistance to IM in 84% and intolerance in 16% (the proportions were similar in dasatinib and nilotinib group, p=0.77). At the time of the present analysis 73 patients (68%) continued second line therapy while in 28 patients (32%) therapy was changed because of resistance or intolerance. Estimated median time for second line therapy withdrawal duration was 35 months. Interestingly, estimated median time to treatment change was significantly longer for dasatinib (42 months) than for nilotinib (29 months) (log-rank test p=0.17). The non-hematological AEs (grade 2-4) were observed in 22 (40%) patients treated with nilotinib and 21 (42%) patients in dasatinib arm (p=0.83). The median estimated time to AE onset was 70 months for nilotinib and 53 months for dasatinib (log-rank test, p=0.35). Vascular events occurred in 8 patients (8%) in both treatment groups, included 6 (11%) in nilotinib group and 2 (4%) in dasatinib group (p=0.16). In nilotinib group one patient with previously diagnosed hypertension developed PAOD which required stent implantation, 2 patients had myocardial infarction, 2 patients had arrythmia and 1 had ischemic stroke. In dasatinib gruoup one patients had myocardial infarction and 1 ischemic stroke. Among other clinically significant AEs pleural effusion (grade 2-4) occurred more often in dasatinib group than in nilotinib group (26% vs. 2%) (p=0.003). Moreover, in dasatinib group two patients (4%) developed pulmonary hypertension, in both cases completely reversible after stopping the drug. In one of these patients sclerodermia was diagnosed before dasatinib treatment. In conclusion we found that despite generalized opinion on good toxicity profile of second generation TKI about 40% of patients treated with second line nilotinib or dasatinib outside clinical studies suffered from grade 2-4 non-hematological AE. It is worth underlining that most AEs occurred late, after more than 2 years of treatment. Importantly, the total frequency of different AEs did not differ significantly and the number of severe vascular events seems comparable on nilotinib and dasatinib, though larger studies may be needed. Disclosures: Gora-Tybor: Bristol Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Robak:Novartis: 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.

Elderly and younger patients with non-small cell lung cancer (NSCLC) derive similar benefit from second-line chemotherapy: A retrospective subset analysis of second-line chemotherapy trials conducted from the Hellenic Cooperative Research Group (HORG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7564-7564
Author(s):  
Sofia Agelaki ◽  
Dora Hatzidaki ◽  
Lampros Vamvakas ◽  
Athanasios G. Pallis ◽  
Athanasios Karampeazis ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Second Line ◽  
Cooperative Research ◽  
First Line ◽  
Second Line Therapy ◽  
Younger Patients ◽  
Second Line Chemotherapy ◽  
Line Therapy ◽  
Significant Difference ◽  
Line Chemotherapy

7564 Background: Elderly patients (pts) achieve a similar survival benefit, with acceptable toxicity, from first-line chemotherapy for the treatment of advanced NSCLC compared with their younger counterparts. There have been no second-line trials specifically designed for elderly pts and few data exist on the efficacy and tolerability of second-line therapy in this population. Moreover, little if any information exists on the frequency of administration of second-line chemotherapy in these pts. Methods: The files of 2004 pts with advanced NSCLC enrolled into first-line chemotherapy trials performed by HORG from 1995 to 2007 were reviewed. A total of 600 pts who received second-line chemotherapy within the context of clinical trials were identified. Patients’ data were analysed for efficacy and toxicity according to age. Results: Second-line chemotherapy was administered in 24% and 34% of pts ≥65 and <65 years old after failure of prior therapy (p=0.0001). A total of 219 (24.8%) of 600 pts who received second-line treatment were ≥65 years old (median age 70 yrs, range 65-82). Response rates to second-line therapy were 11.9% for older pts compared to 12.3% for younger pts (p=ns). TTP was 2.8 and 3.1 months for older and younger pts, respectively (p=ns). Elderly pts receiving second-line chemotherapy had a median survival of 7.7 months compared with 8.2 months for younger pts (p=ns). Similar rates of haematological and non-haematological toxicities were encountered between the two groups. Conclusions: The participation of elderly pts to second-line chemotherapy trials was lower compared to younger patients. There was no significant difference in outcome or toxicity between elderly and younger pts. For elderly pts with advanced NSCLC and good performance status, second-line chemotherapy is appropriate. However, specific second-line trials in older pts are required since those included in the current analysis were probably highly selected to fit the inclusion criteria.

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