Evaluation of the absolute lymphocyte count as a biomarker for melanoma patients treated with the commercially available dose of ipilimumab (3mg/kg).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8575-8575 ◽  
Author(s):  
Michael Andrew Postow ◽  
Jianda Yuan ◽  
Katherine Panageas ◽  
Kita Bogatch ◽  
Margaret Callahan ◽  
...  
Keyword(s):  
Survival Data ◽  
Lymphocyte Count ◽  
Preliminary Finding ◽  
Absolute Lymphocyte Count ◽  
Phase Iii ◽  
Cancer Center ◽  
Karnofsky Performance Score ◽  
Phase Iii Trials ◽  
Pre Treatment

8575 Background: Ipilimumab (ipi) has demonstrated an overall survival (OS) benefit in 2 phase III trials. Only ~30% of patients (pts) achieve clinical benefit, and factors that determine which pts benefit are unclear. For pts treated with 10mg/kg of ipi, we previously reported that an absolute lymphocyte count (ALC) ≥1000/μL prior to dose 3 [week (wk) 7] was associated with improved OS. Since the mean increase in ALC during ipi treatment correlates with dose, we investigated if ALC is also associated with improved OS at 3mg/kg, the currently FDA approved, commercially available dose. Methods: In an IRB-approved analysis, we evaluated landmark survival data from 137 pts treated with 3mg/kg of ipi at Memorial Sloan-Kettering Cancer Center. 67 pts were treated on an expanded access protocol (CA 184-045). 70 pts were treated per FDA approval (commercial ipi) with 4 standard induction doses. These 2 groups were analyzed separately because some pts in CA 184-045 received re-induction ipi. ALC was determined at first ipi dose (baseline, wk 1) and at subsequent doses (wks 4, 7, and 10). Results: Pts treated with 3mg/kg on CA 184-045 with a wk 7 (prior to dose 3) ALC ≥1000/µL had significantly improved OS compared to pts with an ALC at wk 7 <1000/μL (Median OS: not reached vs. 4.24 mos, p<0.001). This OS difference was also seen for pts treated with commercial ipi (Median OS: not reached vs. 4.44 mos, p<0.01). This difference remained significant in a multivariable model accounting for Karnofsky performance score, LDH, M-stage, and number of prior therapies for pts in the CA 184-045 group and commercial ipi group (p=0.01 and p=0.05, respectively). Baseline ALC ≥1000/µL was associated with improved OS (p=0.02) for pts in the commercial ipi group, though follow-up is limited. Conclusions: At the FDA approved dose of ipi, 3mg/kg, ALC at wk 7 remains significantly associated with improved OS. Our preliminary finding of improved OS for pts treated with commercial ipi whose pre-treatment baseline ALC ≥1000/µL deserves confirmation with longer follow-up and prospective validation. Baseline or on treatment ALC may be a marker of overall prognosis, regardless of therapy.

Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 204-204
Author(s):  
Keisho Chin ◽  
Ken Kato ◽  
Byoung Chul Cho ◽  
Masanobu Takahashi ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Subgroup Analysis ◽  
Survival Data ◽  
Special Interest ◽  
Safety Data ◽  
Phase Iii ◽  
Taxane Chemotherapy ◽  
Favorable Safety ◽  
Safety Signals

204 Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ESCC. Herein, we report the three-year survival data of Nivo in ESCC. Methods: In ATTRACTION-3, 419 patients with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT were randomized in a 1:1 ratio to receive Nivo (N = 210) or the investigator’s choice of CT (paclitaxel or docetaxel) (N = 209) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). A subgroup analysis of OS according to the best overall response (BOR) was performed. The onset of treatment-related adverse events of special interest over time in the Nivo arm was also evaluated. Results: As of data cut-off on 25 May 2020, 3 years after the last patient was enrolled, the median OS (mOS) was 10.91 months with Nivo versus 8.51 months with CT [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.64-0.97]. The OS rates of patients with Nivo and CT were 20.2 % and 13.5 % at 24 months, and 15.3% and 8.7% at 36 months, respectively. In the subgroup analysis of OS by BOR, mOS in CR/PR patients were 19.91 and 15.41 months (HR 0.84, 95%CI 0.46-1.54) and that in SD patients were 17.38 and 9.36 months (HR 0.45, 95%CI 0.26-0.78) in the Nivo and CT arm, respectively. Furthermore, mOS in PD patients were 10.91 and 6.18 months (HR 0.56, 95%CI 0.33-0.95) in the Nivo and CT arm, respectively. No new safety signals were detected during the three-year follow-up. Time to onset of the event of special interest was within the range of events previously observed in other indications. Conclusions: At three-year follow up, Nivo continued to show improved OS over CT in pretreated patients with advanced ESCC patients. Nivo showed a longer mOS than CT regardless of BOR. During the three-year follow-up, no new safety signals were observed. Clinical trial information: NCT02569242.

A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Wang Fang FangZheng
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Long Term Outcomes ◽  
First Line ◽  
Grade 3

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

scholarly journals Evaluating Intermittent Androgen-Deprivation Therapy Phase III Clinical Trials: The Devil Is in the Details

2016 ◽  
Vol 34 (3) ◽  
pp. 280-285 ◽  
Author(s):  
Maha Hussain ◽  
Catherine Tangen ◽  
Celestia Higano ◽  
Nicholas Vogelzang ◽  
Ian Thompson
Keyword(s):  
Prostate Cancer ◽  
Statistical Power ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
End Point ◽  
Phase Iii Clinical Trials ◽  
Noninferiority Trials ◽  
Phase Iii Trials

Purpose Intermittent androgen deprivation (IAD) has been widely tested in prostate cancer. However, phase III trials testing continuous androgen deprivation (CAD) versus IAD have reached inconclusive and seemingly contradictory results. Different design and conduct issues must be critically evaluated to better interpret the results. Patients and Methods Seven published phase III trials were examined for prespecified design and outcomes. Treatment specifications; primary end point; superiority versus noninferiority design assumptions, including magnitude of assumed versus observed noninferiority margin (NIM); duration of follow-up; and quality-of-life (QOL) outcomes were considered in terms of the results and conclusions reported. Results Five trials had a superiority and three had a noninferiority primary hypothesis. Only three trials had a uniform population and overall survival (OS) end point. All trials observed better outcomes in terms of OS and progression-free survival (PFS) than assumed at time of study design, translating into prespecified NIMs or hazard ratios that reflected larger absolute differences in OS or PFS between arms. Lower-than-expected event rates also reduced statistical power for the trials. Other factors, including length of follow-up, cause of death, QOL, and primary end point, and their impact on trial interpretation are discussed. Conclusion No trial to date has demonstrated survival superiority of IAD compared with CAD. Trials concluding IAD is noninferior to CAD were based on wide NIMs that included clinically important survival differences, not likely to be considered comparable by physicians or patients. Interim analyses relying on short follow-up and including a majority of non–prostate cancer deaths will favor a noninferiority conclusion and should be interpreted cautiously. Adequate follow-up is required to ensure capture of prostate cancer deaths in both superiority and noninferiority trials.

040 An analysis of malignancy risk in the clinical development programme of cladribine tablets in patients with relapsing multiple sclerosis

2018 ◽  
Vol 89 (6) ◽  
pp. A17.1-A17
Author(s):  
Andrew Galazka ◽  
Axel Nolting ◽  
Stuart Cook ◽  
Thomas Leist ◽  
Giancarlo Comi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Case Reports ◽  
Meta Analysis ◽  
Reference Population ◽  
Phase Iii ◽  
Disease Modifying Drugs ◽  
Malignancy Risk ◽  
Phase Iii Trials ◽  
Relapsing Multiple Sclerosis

IntroductionAn independent meta-analysis; Pakpoor et al. Neurol Neuroimmunol Neuroinflamm 2015;2:e158) in Phase III trials (with a 2 year duration) of disease modifying drugs (DMDs) in patients with relapsing multiple sclerosis found no increased rate of malignancy with cladribine tablets (CT) versus other DMD treatments. Data from additional trials involving CT 3.5 mg/kg (CT3.5) and a safety registry (up to 8 years’ follow-up) allow further insights into malignancy risk. Objective is to assess malignancy risk with CT3.5 monotherapy and placebo (PBO) in data from 3 Phase III trials and a registry, and compare the incidence rate with a global database.MethodsThe CT 3.5 population comprised 923 patients (3433 patient-years’ [PY] total exposure time) and the PBO group comprised 641 patients (2026 PY). Individual case reports of malignancies were reviewed by independent, blinded adjudication committee. Standardised incidence ratios (SIR) were calculated using the GLOBOCAN reference population (excluding non-melanoma skin cancers [NMSCs]) and a Danish reference population for NMSC rates.ResultsThe incidence per 100 PY of confirmed malignancy was CT3.5 0.293 (95%CI 0.158–0.544) and PBO 0.148 (95%CI 0.048–0.460); the risk difference 95% CI included 0 (−0.166–0.414). The CT 3.5 malignancy SIR was almost identical (0.97, 95% CI 0.44–1.85) to the GLOBOCAN matched reference population. The PBO group SIR was numerically lower (0.48, 95% CI 0.14–1.53). There were no cases of haematological, lymphoproliferative or virus-induced cancers. There was no clustering of specific tumour types, and the incidence of skin cancer was not increased after treatment with CT3.5 versus PBO. The incidence of malignancies with CT3.5 was constant and did not increase over time.ConclusionAnalysis of malignancy rates in a cohort that includes patients with up to 8 years’ follow-up confirms the Conclusion of the earlier meta-analysis; the incidence of malignancies with CT3.5 is similar to a matched reference population.

Prognostic Relevance of Monocytopenia and Lymphocyte-to-Monocyte Ratio in Primary Myelodysplastic Syndromes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1996-1996
Author(s):  
Lyla Saeed ◽  
Mrinal M Patnaik ◽  
Kebede H. Begna ◽  
Aref Al-Kali ◽  
Mark R Litzow ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Lymphocyte Count ◽  
Research Funding ◽  
Prognostic Value ◽  
Leukocyte Count ◽  
Multivariable Analysis ◽  
Absolute Lymphocyte Count ◽  
Monocyte Count ◽  
Lymphocyte To Monocyte Ratio

Abstract Background We have previously shown an independent adverse prognostic effect of lymphopenia (absolute lymphocyte count <1.2 x 10(9)/L) for survival in MDS (Jacobs et al. Am J Hematol 2010;85:160) whereas others have suggested a similar value from lymphocyte-to-monocyte ratio (LMR); patients with LMR ≥5 experienced shorter survival with median 67 vs. 126 months (Mushtaq et al. JCO May 20 Supp. 2016:7062). Whether or not "monocytopenia" also carries a prognostic value in MDS is currently unknown and was the main objective for the current study, which also addresses the prognostic value of LMR. Methods We retrospectively recruited 889 consecutive patients with primary MDS who were untreated at the time of referral to our institution and in whom absolute monocyte count (AMC) and absolute lymphocyte count (ALC) at time of referral were documented. The diagnosis of MDS and leukemic transformation (LT) was made according to WHO criteria (Blood. 2009;114:937). Complete follow-up information was updated in January 2015. For the purposes of the current study, monocytopenia was defined as AMC below the lower limit of the institutional normal range, which was 0.3 to 0.9 x 10(9)/L. Comparisons of survival and other clinical parameters were performed between i) patients with and without monocytopenia and ii) patients with and without LMR ≥5. Conventional methods were used for statistical analysis. Results Patient characteristics: Median (range) values for the 889 study patients (69% males) included: age 72 (18-98), hemoglobin 9.6 g/dL (5.4-15.7), leukocyte count 3.4 x 10(9)/L (0.4-35), platelet count 106 x 10(9)/L (2-1804), circulating blasts 0% (0-18), bone marrow blasts 3% (0-19) and absolute lymphocyte count (ALC) 1.2 x 10(9)/L (.02-8.9). Transfusion need was documented in 33% of patients and abnormal cytogenetics in 49%. Risk stratification by the revised international prognostic scoring system (IPSS-R) was very high in 11%, high in 16%, intermediate in 21%, low in 36% and very low in 16%. The median (range) AMC for the entire study population of 889 patients was 0.22 x 10(9)/L (0.0-1.8).The number of patients with subnormal AMC was 539 (61%). After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformations were documented. Comparison of patients stratified by absolute monocyte count and LMR Compared to patients with AMC >0.3 x 10(9)/L, MDS patients with monocytopenia displayed younger age (p<0.0001), lower hemoglobin (p=0.005), higher red blood cell transfusion need (p=0.03), lower leukocyte count (p<0.0001), lower platelet count (p<0.0001), lower absolute neutrophil count (p<0.0001), higher circulating (p=0.03) and bone marrow (p<0.0001) blasts, higher incidence of abnormal karyotype (p=0.03), and higher risk distribution in terms of both IPSS-R (p<0.0001) and cytogenetic risk stratification by IPSS-R (p=0.03). In univariate analysis, lower AMC was associated with inferior survival (p=0.002); significance was even more apparent when comparing patients with and without monocytopenia (p=0.0003; HR 1.3, 95% CI 1.1-1.5). Similarly, there was significant association between LMR and survival (p<0.0001) with patients with LMR ≥5 experiencing inferior survival (p=0.03; HR 1.2; 95% CI 1.02-1.4). In multivariable analysis, the adverse effect of monocytopenia was shown to be independent of age (p<0.0001), gender (p=0.0001), anemia (Hemoglobin <10 g/dL; p=0.002), thrombocytopenia (platelets <100 x 10(9)/L; p=0.01), neutropenia (absolute neutrophil count <0.8 x 10 (9)/L; p=0.005), subnormal ALC (p=0.0008), circulating blast percentage (p=0.002), cytogenetic risk stratification by IPSS-R (p=0.006) and LMR (p=0.02) or LMR ≥5 (p=0.002); however, significance was lost when risk stratification by IPSS-R was added to the multivariable analysis (p=0.7). In regards to LMR, it retained its significance (p=0.009) during multivariable analysis that included monocytopenia or subnormal ALC, as covariates; however, significance was lost in the context of IPSS-R (p=0.24 for LMR and 0.8 for LMR ≥5) Conclusions Monocytopenia in MDS clusters with adverse disease features and both monocytopenia and higher LMR were associated with poor survival. Despite the display of prognostic independence from each other and other risk factors considered individually, the survival impact of neither monocytopenia nor LMR was found to be independent of IPSS-R. Disclosures Al-Kali: Novartis: Research Funding; Celgene: Research Funding.

Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21040-21040
Author(s):  
R. Trujillo ◽  
E. Gallego ◽  
A. Márquez ◽  
N. Ribelles ◽  
J. Trigo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Phase Iii ◽  
Rank Test ◽  
Prognostic Effect ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Her 2

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.

Long-term follow-up of autotransplant (AT)-supported high-dose melphalan (hdm) for multiple myeloma (MM): Update of Intergroup Francophone du Myelome (IFM), Southwest Oncology Group (SWOG), and Arkansas (ARK) Total Therapy (TT) trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8519-8519
Author(s):  
B. Barlogie ◽  
M. Attal ◽  
J. Crowley ◽  
J. Harousseau
Keyword(s):  
Phase Iii ◽  
Long Term Results ◽  
High Dose ◽  
Long Term Follow Up ◽  
Phase Iii Trials ◽  
Trial Outcomes ◽  
Total Therapy ◽  
High Dose Melphalan

8519 Background: Clinical trial outcomes are usually published when statistical protocol objectives have been met, with short median follow-up not exceeding 5 years. Due to treatment innovations, MM survival beyond 10 years has become more common but formal long-term results are seldom reported. Methods: IFM, SWOG and ARK provide an update of their major trials. IFM-90: 1 AT v standard therapy (STD), IFM-94: 2 v 1 AT, IFM-9902: 2AT ± THAL, IFM-9904: 2AT for high-risk MM; SWOG-9321: 1 AT v STD; TT1: 2 AT with interferon, TT2: 2AT ± THAL, TT3: 2AT + THAL + bortezomib. Results: OS clustered in 3 groups with superior outcomes for TT3/TT2/IFM-99 v TT1 v IFM-94/ IFM-90/SWOG-9321 with 5/10/15-yr estimates of 70%/50%/TE v 57%/35%/20% v 43%/25%/15% (p<0.0001). EFS also clustered in 3 groups with superior outcomes for TT3 v TT2 v remainder with estimates of 71%/TE/TE v 50%/35%/TE v 27%/ 15%/10% (p<0.0001). Among phase III trials, added THAL in TT2 increased 10-yr OS/EFS from 40%/25% to 60%/40% (p=0.04/p=0.0005); 10-yr OS was 30% v 8% with 1 v 0 AT in IFM-90 (p=0.005), 31% v 21% with 2 AT v 1 AT in IFM-94 (p=0.08), and 20% for both arms of S9321. On multivariate analysis involving 2962 patients, OS was adversely affected by B2M >=3.5mg/L (p<0.001), LDH >=ULN (p<0.001), hemoglobin <10g/dL (p=0.001) and albumin <3.5g/dL (p=0.02). 2AT (65%) and THAL (21%) both contributed independently to superior OS (p<0.001, p=0.002); among individual trials, IFM-9902 (19%) and TT2/TT3 (33%) both improved OS significantly (both p<0.001). For each of the 3 major OS clusters, 228 patients could be matched on B2M, LDH, hemoglobin and albumin, with 10-yr OS/EFS estimates of 65%/30% for the TT3/TT2/IFM-9902 group significantly exceeding 30%/15% each for the other 2 groups (p=0.001/p=0.001). Conclusions: A 15-yr EFS plateau of 10% with older trials and superior 10-yr EFS/OS estimates of 50%/35% with recent studies emphasize that cure should be a realistic trial objective in contemporary MM therapy, requiring however very long-term follow-up beyond 15 years. [Table: see text]

Survival analysis of maintenance therapy with capecitabine (Cape) in patients with resected pancreatic adenocarcinoma (PAC) after adjuvant therapy: A retrospective cohort study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14658-e14658
Author(s):  
Xuezhong Yang ◽  
Benjamin Weinberg ◽  
Jimmy J. Hwang ◽  
Christina Sing-Ying Wu ◽  
Madeeha Akram ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Maintenance Therapy ◽  
Survival Data ◽  
Prolonged Exposure ◽  
Cancer Center ◽  
Control Group ◽  
Study Group

e14658 Background: The 5-year survival of PAC with surgery alone is below 10%, and with adjuvant chemotherapy increases to about 20%. The original GITSG adjuvant study demonstrating a survival benefit compared to surgery could be attributed to the use of 2-years of weekly IV bolus 5FU, and not only chemoradiation. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that may remain in G0 arrest, by attacking them as they infrequently enter G1/S phase. To evaluate this hypothesis, we retrospectively evaluated our pts who were treated with or without maintenance Cape. Methods: Pts in the Georgetown/Lombardi Cancer Center EMR since Oct 2007 were sought for PAC that was resected with curative intent, received standard adjuvant chemotherapy with or without chemoradiation. The study group received maintenance cape for at least 2 months, and the control group was monitored until disease recurrence. Only pts with complete follow-up survival data were analyzed. Results: 20 pts met the criteria as study group, and 58 pts as the control group. In the study group, cape was usually given 1000mg orally twice a day, Monday through Friday following adjuvant therapy, for an indefinite period, up to 2 years. Pts received cape for median duration of 12.5 months (2 to 24 months), and the median follow-up duration was 33 months (16 to 78 months). The median overall survival (OS) for the study group was 48 months. The 2 year OS was 94%, and 5 year OS was 40%. The median recurrence free survival (RFS) was 39 months. The 2 year RFS was 67%, and the 5 year RFS was 25%. Common toxicities were mild hand-and-foot syndrome and fatigue. 4 pts discontinued cape due to toxicities: febrile neutropenia, severe fatigue, weight loss and diarrhea. The control group was of comparable staging, and the median OS was 22 months, 5 year OS rate was 16%, median RFS was 13 months, 2 year RFS was 19%. Conclusions: In this single institute retrospective controlled cohort study, Cape maintenance therapy following adjuvant therapy in resected PAC is associated with a significantly (p<0.05) higher OS and PFS compared to the control group. This approach should be studied in a RCT.

Treatment of adenocortical carcinoma: 11-year Birmingham experience.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 462-462
Author(s):  
Lenka Zvirinska ◽  
Alice Tew ◽  
Emilio Porfiri
Keyword(s):  
Survival Data ◽  
Standard Treatment ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Limited Efficacy ◽  
Significant Difference ◽  
Unselected Population ◽  
Group 3 ◽  
Time To Relapse

462 Background: Due to the lack of prospective randomized phase III trial data, we have analysed patients with ACC treated between 2000 and 2011. Methods: All the patients given Mitotane (standard treatment of ACC in UHB, Birmingham) where extracted from pharmacy database. Results: 23 patients were identified, age 26-74 (median 53). Follow-up for whole group was 14–167m, median 60. Overall survival (OS) was 3-48m, medium 11.1 patient with slowly growing disease is still alive (167m) with 2nd dg of breast cancer. 19 patients were treated for metastatic disease, 4 in adjuvant setting. 7 patients were managed by endocrinologist only (3 adjuvant, 2 poor PS, 1 reluctant to treatment and 1 details unknown). 16 patients were under shared care. 4 these patients were never exposed to chemotherapy (2 poor PS, 1 returned to Africa, died within 5 months, 1 declined chemotherapy, still alive at 16 months post). 6/19 metastatic patients had chemotherapy as 1st treatment (4 patients etoposide/doxorubicin/cisplatin chemotherapy, 1 etoposide/carboplatin, 1 etoposide/cisplatin), 7 were treated with chemotherapy on PD(6 streptozocin, 1 etoposide/doxorubicin/cisplatin, 1 etoposide/cisplatin). There was no significant difference in OS when those approaches were compared (1st group 7-16 m, median 10, 2nd group 3-14, median 11) But TTP has been slightly worse for treatment on PD as expected (1st group 3-13m, median 6.5; 2nd group 3-14, median 3), although might be due to tendency to use Streptozocin, consistant with preliminary published results of FIRMACT trial.3 patients were treated with 2 lines of chemotherapy (age 30,31, 38), TTP 2- 5 m. Adjuvant patients within our sample has been followed up for limited perion only (11 – 71m, median 22.5), however no recurrence was diagnosed so far.In metastatic patient population 4 patients were treated for recurrence with time to relapse 3-43m, medium 23.5. Conclusions: ACC is heterogenic disease as confirmed by our survival data. In unselected population median OS is comparable to FIRMACT. Consistant with literature review, chemotherapy threatment can be delivered as 1st-line or delayed till PD. 2nd-line chemotherapy is of limited efficacy.

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