Weekly Irinotecan in Patients with Metastatic Colorectal Cancer Failing 5-Fluorouracil-Based Chemotherapy: Efficacy and Prognostic Factors

2003 ◽  
Vol 89 (2) ◽  
pp. 141-145 ◽  
Author(s):  
Aziz Karaoğrlu ◽  
Suayib Yalcin ◽  
Gülten Tekuzman ◽  
Ayse Kars ◽  
Ismail Çelik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Objective Response ◽  
Response Duration ◽  
Response To Treatment ◽  
Time To Progression ◽  
Median Response ◽  
Poor Prognostic Factor ◽  
Histologic Subtype

Aims and background We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. Methods A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. Results A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (≤45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. Conclusions We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

scholarly journals Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab

2014 ◽  
Vol 32 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
Suzanne L. Topalian ◽  
Mario Sznol ◽  
David F. McDermott ◽  
Harriet M. Kluger ◽  
Richard D. Carvajal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Response Duration ◽  
Advanced Melanoma ◽  
Immune Memory ◽  
Drug Discontinuation ◽  
Median Response ◽  
The Impact

PurposeProgrammed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued.Patients and MethodsPatients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation.ResultsMedian overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative.ConclusionOverall survival following nivolumab treatment in patients with advanced treatment–refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas

2004 ◽  
Vol 22 (23) ◽  
pp. 4762-4771 ◽  
Author(s):  
Maria A. Kouvaraki ◽  
Jaffer A. Ajani ◽  
Paulo Hoff ◽  
Robert Wolff ◽  
Douglas B. Evans ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response To Treatment ◽  
Rank Test ◽  
Median Response ◽  
Log Rank Test

Purpose The role of systemic chemotherapy in the management of pancreatic endocrine carcinoma (islet cell carcinoma; PEC) is an area of considerable controversy. Response rates ranging from 6% to 69% have been reported for streptozocin-based chemotherapy. We retrospectively studied 84 patients with locally advanced or metastatic PEC who had been treated with fluorouracil, doxorubicin, and streptozocin (FAS) to determine the objective response rate, duration of progression-free survival (PFS), and duration of overall survival (OS). Patients and Methods Eligible patients had histologic or cytologic confirmation of their tumor and measurable disease on computed tomography or magnetic resonance imaging scans. Response to treatment was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee. Results Sixty-one of the patients were male and 23 were female, with a median age of 54 years (range, 24 to 78 years). The response rate (RR) to FAS was 39%, with a median response duration of 9.3 months. The 2-year PFS rate was 41%, and the 2-year OS rate was 74%. The extent of liver metastatic disease correlated with a worse PFS (P = .01 by log-rank test) and a worse OS (P < .0001 by log-rank test). Analyses showed that metastatic replacement of more than 75% of the liver and prior chemotherapy were independently associated with inferior PFS. Conclusion Patients with locally advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and responders may experience longer PFS and OS. The volume of metastases in the liver is the most important predictor of outcome.

scholarly journals Perspectives and controversies in the treatment of advanced colorectal cancer: From paliation to cure

2002 ◽  
Vol 49 (2) ◽  
pp. 37-39
Author(s):  
Ivan Popov
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Advanced Colorectal Cancer ◽  
Clinical Status ◽  
Objective Response ◽  
Tumor Burden ◽  
New Drugs ◽  
Time To Progression ◽  
History Of

Advanced colorectal cancer (ACRC) has been traditionally considered resistant to chemotherapy, with no clear benefit in relation to time to progression and overall survival. Nevertheless, nowadays first and second line therapeutic approaches have dramatically changed the natural history of ACRC, and that means that at present the most important decision in a patient is not to treat or no to treat with chemotherapy, but to choose the best chemotherapy schedule at any time. Following this purpose it has been necessary, not only the emergence of new drugs and schedules, but also the understanding of the clinical efficacy. Actually, to the classic parameters such as, objective response, time to progression, and overall survival, new parameters studying clinical benefit have been added. Among these new parameters we can find the weight loss, symptom-free period, quality of life, pain-free interval, etc. Therefore, the really important aim in these situations is the patient clinical status, being less important the survival or the tumor burden reduction.

Randomized Phase II Study of Two Irinotecan Schedules for Patients With Metastatic Breast Cancer Refractory to an Anthracycline, a Taxane, or Both

2004 ◽  
Vol 22 (14) ◽  
pp. 2849-2855 ◽  
Author(s):  
Edith A. Perez ◽  
David W. Hillman ◽  
James A. Mailliard ◽  
James N. Ingle ◽  
J. Michael Ryan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Response Duration ◽  
Median Response

Purpose A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules. Patients and Methods MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m2 weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m2 every 3 weeks. Results The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with ≥ 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm. Conclusion Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.

Capecitabine combined with oxaliplatin (XELOX) as first-line chemotherapy in colorectal cancer with liver metastases

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15146-e15146
Author(s):  
H. Mahfouf ◽  
H. Djeddi ◽  
S. Belhadef ◽  
K. Bouzid ◽  
K. Bentabak
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Liver Metastases ◽  
Objective Response ◽  
Response Duration ◽  
Hepatic Function ◽  
Metastatic Colorectal Carcinoma ◽  
Median Response ◽  
Efficacy Analysis ◽  
Intent To Treat

e15146 Background: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated. Methods: Chemotherapy-naive patients confirmed histologic colorectal cancer with liver metastases, adequate born morrow, renal and hepatic function, measurable diseases were considered eligible for the study. Treatment: Six cycles of oxaliplatin 85 mg/m2 day1 plus capecitabine 1250 mg/m2 twice daily days 1–14 every 21 days Results: Twenty six patients were evaluated for safety and efficacy (male/female, 12/14). Median age was 53 years (range 32–75 years). A total of 142 cycles have been administered: median per patient 4 (range 3–6 courses). In an intent-to-treat efficacy analysis, One complete and ten partial responses were achieved [overall objective response rate (ORR): 42, 3%; whereas 7 patients had stable disease and eight patients had progressive disease. Seven patients from 11 with objective response underwent major liver resection: 2 bisegmentectomy, 1 left lobectomy, 4 segmentectomy, and receive the same regimen of chemotherapy (Six cycles) as an adjuvant treatment and still alive without recurrence. The overall survival (OS) was 19, 2 months. The median response duration was 7 months. The median time to progression (TTP) was 8 months. The grade 3 toxicities were diarrhea (7%), fatigue (4%), neurotoxicity (2%), neutropenia (2%), and thrombocytopenia 4%). Conclusions: The combination of oxaliplatin and capecitabine is safe and has a promising activity in patients with liver metastatic colorectal carcinoma. No significant financial relationships to disclose.

Irinotecan in Combination With Fluorouracil in a 48-Hour Continuous Infusion As First-Line Chemotherapy for Elderly Patients With Metastatic Colorectal Cancer: A Spanish Cooperative Group for the Treatment of Digestive Tumors Study

2005 ◽  
Vol 23 (15) ◽  
pp. 3545-3551 ◽  
Author(s):  
Javier Sastre ◽  
Eugenio Marcuello ◽  
Bartomeu Masutti ◽  
Matilde Navarro ◽  
Silvia Gil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Continuous Infusion ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Response To Treatment

Purpose Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. Patients and Methods Patients ≥ 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. Results By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. Conclusion Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.

Age-specific prognostic factors in patients treated surgically for pulmonary metastases of colorectal cancer: A multi-institutional cumulative follow-up study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 773-773
Author(s):  
Sayumi Nakao ◽  
Michio Itabashi ◽  
Mamiko Ubukata ◽  
Yoshiko Bamba ◽  
Tomoichiro Hirosawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Pulmonary Resection ◽  
Lung Resection ◽  
Colorectal Metastases ◽  
Pulmonary Metastasectomy ◽  
Poor Prognostic Factor ◽  
Elder Patients

773 Background: The aim of this study was to investigate the age-specific prognostic factors for overall survival (OS) and disease-free interval (DFI) after pulmonary metastasectomy for colorectal cancer (CRC). Methods: We performed a retrospective analysis of 1,179 patients who underwent lung resection for colorectal metastases from 2001 to 2012 in 109 affiliated institutions of the Japanese Society for Cancer of the Colon and Rectum study group. The patients were divided into three groups by the age at pulmonary resection: Group A (GA) comprised of 396 patients who underwent lung resection under the age of 60 years old; Group B (GB) comprised of 604 patients who underwent lung resection between the ages of 61 and 74 years old; Group C (GC) comprised of 179 patients who underwent lung resection over the age of 75 years old. We used the Cox proportional hazard regression to identify independent prognostic factors for OS and DFI. Results: Median OS times after pulmonary resection were 45 months, 43 months, and 43 months for GA, GB, and GC, respectively. Two-year and 5-year overall survival rates were 73% and 54% for GA, 77% and 63% for GB, and 82% and 68% for GC, respectively. The independent unfavorable prognostic factors were recurrence after pulmonary resection (p<0.0001) in GA, detection of liver metastases before lung resection (p=0.0126), a high level of carcinoembryonic antigen (p=0.0003), and recurrence after pulmonary resection (p<0.0001) in GB, and recurrence after pulmonary resection (p<0.0001) in GC. Median DFI times were 11 months in all groups. The independent unfavorable prognostic factor was a removal of mediastinal lymph node (p=0.0335) in GB. Conclusions: Elder patients (GC) showed nearly the same OS rate compared with non-elder patients (GB), while younger patients (GA) showed poor OS rate. Recurrence after pulmonary resection revealed to be a poor prognostic factor in all groups.

scholarly journals Germline Mutations in Other Homologous Recombination Repair-Related Genes Than BRCA1/2: Predictive or Prognostic Factors?

2021 ◽  
Vol 11 (4) ◽  
pp. 245
Author(s):  
Laura Cortesi ◽  
Claudia Piombino ◽  
Angela Toss
Keyword(s):  
Prognostic Factors ◽  
Homologous Recombination ◽  
Pancreatic Adenocarcinoma ◽  
Objective Response ◽  
Metastatic Breast ◽  
Germline Mutations ◽  
Response To Treatment ◽  
Homologous Recombination Repair ◽  
Dna Breaks ◽  
Recombination Repair

The homologous recombination repair (HRR) pathway repairs double-strand DNA breaks, mostly by BRCA1 and BRCA2, although other proteins such as ATM, CHEK2, and PALB2 are also involved. BRCA1/2 germline mutations are targeted by PARP inhibitors. The aim of this commentary is to explore whether germline mutations in HRR-related genes other than BRCA1/2 have to be considered as prognostic factors or predictive to therapies by discussing the results of two articles published in December 2020. The TBCRC 048 trial published by Tung et al. showed an impressive objective response rate to olaparib in metastatic breast cancer patients with germline PALB2 mutation compared to germline ATM and CHEK2 mutation carriers. Additionally, Yadav et al. observed a significantly longer overall survival in pancreatic adenocarcinoma patients with germline HRR mutations compared to non-carriers. In our opinion, assuming that PALB2 is a high-penetrant gene with a key role in the HRR system, PALB2 mutations are predictive factors for response to treatment. Moreover, germline mutations in the ATM gene provide a better outcome in pancreatic adenocarcinoma, being more often associated to wild-type KRAS. In conclusion, sequencing of HRR-related genes other than BRCA1/2 should be routinely offered as part of a biological characterization of pancreatic and breast cancers.

Sorafenib in Combination With Gemcitabine in Recurrent Epithelial Ovarian Cancer: A Study of the Princess Margaret Hospital Phase II Consortium

2010 ◽  
Vol 20 (5) ◽  
pp. 787-793 ◽  
Author(s):  
Stephen A. Welch ◽  
Hal W. Hirte ◽  
Laurie Elit ◽  
Russel J. Schilder ◽  
Lisa Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Stable Disease ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Ca 125 ◽  
Response Evaluation ◽  
Time To Progression ◽  
Response Evaluation Criteria

Objectives:Antiangiogenic strategies have demonstrated efficacy in epithelial ovarian cancer (EOC). Sorafenib is a novel multitargeted kinase inhibitor with antiangiogenic activity. Gemcitabine has known activity against EOC. A phase 1 clinical trial of this combination suggested activity in ovarian cancer with no dose-limiting toxicity. This phase 2 study was designed to examine the safety and efficacy of gemcitabine and sorafenib in patients with recurrent EOC.Methods:Patients with recurrent EOC after platinum-based chemotherapy and who had subsequently received up to 3 prior chemotherapy regimens were eligible. Gemcitabine (1000 mg/m2 intravenous [IV]) was administered weekly for 7 of 8 weeks in the first cycle, then weekly for 3 weeks of each subsequent 4-week cycle. Sorafenib (400 mg p.o. bid) was given continuously. The primary end point for this trial was objective response rate by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included Gynecologic Cancer Intergroup (GCIG) CA-125 response, time to progression, overall survival, and toxicity.Results:Forty-three patients were enrolled, and 33 completed at least 1 cycle. Two patients had a partial response (Response Evaluation Criteria in Solid Tumors objective response rate = 4.7%). Ten patients (23.3%) maintained response or stable disease for at least 6 months. GCIG CA-125 response was 27.9%. The median time to progression was 5.4 months, and the median overall survival was 13.0 months. Hematologic toxicity was common but manageable. The most common nonhematologic adverse events were hand-foot syndrome, fatigue, hypokalemia, and diarrhea.Conclusion:This trial of gemcitabine and sorafenib in recurrent EOC did not meet its primary efficacy end point, but the combination was associated with encouraging rates of prolonged stable disease and CA-125 response.

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