Improved Leukemia-Free Survival after Post-Consolidation Treatment with Histamine Dihydrochloride and Interleukin-2 in AML: A Randomized Phase III Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 261-261 ◽  
Author(s):  
Mats Brune ◽  
Sylvie Castaigne ◽  
John Catalano ◽  
Kurt Gehlsen ◽  
Wolf-Karsten Hofmann ◽  
...  
Keyword(s):  
Low Dose ◽  
Interleukin 2 ◽  
Phase Iii ◽  
Rank Test ◽  
Consolidation Therapy ◽  
Histamine Dihydrochloride ◽  
Free Survival ◽  
Consolidation Treatment ◽  
Log Rank Test ◽  
Significant Difference

Abstract Background: Histamine dihydrochloride (HDC) potentiates immune-based therapies by protecting pivotal anti-neoplastic lymphocytes from phagocyte-induced suppression. Previous results in AML indicated that post-consolidation treatment with HDC and low-dose interleukin-2 (IL-2) is safe and feasible, and that the combination may prolong leukemia-free survival (LFS). Aims: The primary objective was to determine if post-consolidation treatment with IL-2 and HDC could improve LFS for AML pts in complete remission (CR). Secondary objectives included overall survival (OS), LFS in CR1 and CR>1 subgroups, and safety. Methods: This international, randomized, open-label, phase III study was conducted at 92 centers. From June 1998 to October 2000, 320 AML pts [148 females, 172 males, median age 57 (18–84) yrs] were enrolled in CR after completion of standard consolidation therapy. Pts were stratified by CR1 or CR>1 and randomized to either treatment (n=160) or no treatment (control, n=160) arms. The treatment was self-administered at home and included 10 cycles of low-dose IL-2 (aldesleukin, Chiron Corp) 18 000 U/kg, sc bid plus HDC (Maxim Pharmaceuticals) 0.5 mg sc bid. For cycles 1–3, each cycle comprised 3 wks of treatment and 3 wks of rest, whereas in cycles 4–10 the rest periods were 6 wks. The study arms were well balanced with respect to age, sex, karyotype-based risk, time from CR to inclusion and frequency of secondary leukemia. Pts were followed for relapse and survival using an identical assessment schedule until 3 yrs after last enrollment. All efficacy analyses were intent-to-treat. Results: The median follow-up of living pts was 46 months. For the primary endpoint, treatment with HDC/IL-2 increased LFS in the entire study population (CR1/CR>1, n=320, p=0.026 stratified log-rank test). There was no significant difference in OS (p=0.33). In the analysis of pre-stratified subgroups, one pt was excluded. For CR1 pts (n=262), HDC/IL-2 significantly improved LFS (p=0.011, log-rank test), with 3-year Kaplan-Meier estimates of 26% (control group) and 40% (treatment group). The difference in OS did not reach significance (p=0.16). For CR>1 pts (n=57), outcome was not affected by treatment. Side effects attributable to IL-2 included fever and local inflammatory reactions. HDC treatment induced symptoms of transient vasodilatation. Serious adverse events occurred in approximately 20% of pts in both groups. There were no treatment-related deaths. Conclusions: For AML pts in CR, post-consolidation therapy with HDC and IL-2 was safe and significantly improved LFS compared to standard of care. The benefit observed of HDC/IL-2 treatment appears to be explained by a reduction of relapses in CR1 pts.

scholarly journals Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial

2020 ◽  
Vol 38 (6) ◽  
pp. 593-601 ◽  
Author(s):  
Shawn Malone ◽  
Soumyajit Roy ◽  
Libni Eapen ◽  
Choan E ◽  
Robert MacRae ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Definitive Treatment ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Grade 3

PURPOSE Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

Adjuvant low-dose interleukin-2 (IL2) plus interferone-alpha (IFN) in operable renal cell cancer (RCC). A phase III, randomized, multicenter, independent trial of the Italian Oncology Group for Clinical Research (GOIRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA5028-LBA5028 ◽  
Author(s):  
R. Passalacqua ◽  
C. Buzio ◽  
S. Buti ◽  
R. Labianca ◽  
C. Porta ◽  
...  
Keyword(s):  
Low Dose ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Phase Iii ◽  
Who Grade ◽  
Free Survival ◽  
Repeated Doses

LBA5028 Background: For pts with non-metastatic RCC, no standard adjuvant treatment exists. Immunotherapy (IT) using IFN and/or IL2 is effective in metastatic disease setting. Low and chronically repeated doses of IL2 plus IFN induce a persistent stimulation of the immune system with no relevant toxicity. Methods: From July1994 to March 2006, surgically treated RCC pts were randomized to the following arms: A) low-dose IT; B) control arm. IT consisted of a 4-week cycle of s.c. IL2 (5 days/wk, 1 million UI/sqm bid d 1,2 and 1 million UI/sqm × 1 d 3,4,5) + IFN (1,8 million UI/sqm d 3,5 of each week). Cycles were repeated every 4 months for the first 2 years and every 6 months for the remaining 3 years. Each patient received 12 cycles in 5 years. Inclusion criteria were as follows: histological diagnosis of RCC, age <75 yrs, radical or partial nephrectomy within the past 3 months, pT1 (diameter of T > 2,5 cm), T2, T3 a-b-c; pN0-pN3, M0; good cardiac and renal function and no autoimmune disease. Based on a planned sample size of 320 pts, the trial was designed to have a 80% power to detect a 15% improvement in 5-year survival. Results: A total of 310 pts were randomized: 157 on arm A, 153 on arm B. Pts characteristics were well balanced between the two arms. At a median follow-up of 52 months, 77 pts relapsed: 35 in arm A and 42 in arm B. In the first 5 years of observation, disease free survival (DFS) curves were similar in the two arms, but diverged thereafter. DFS at 5 and 10 years was 0.73 and 0.73 in arm A vs 0.73 and 0.60 in arm B with an estimated Hazard Ratio (HR) of 0.84 (95% CI: 0.54–1.33 p=0.47). Efficacy of IT was more evident in patients with good PS (HR 0.78; 0.47–1.30 p=0.35); age<60 yrs (HR 0.61; 0.31–1.19 p=0.15), and low tumor grade (HR 0.70; 0.38–1.27 p=0.24). As for overall survival, 59 deaths were observed with no differences between the two arms. Toxicity was mild and limited to WHO grade 1 or 2 in the majority of cases. Conclusions: Low-dose adjuvant IL2+IFN is feasible in RCC and seems to reduce the risk of recurrence after 5 years from diagnosis. Follow-up update is still ongoing. No significant financial relationships to disclose.

Is RECIST-defined progression free-survival a meaningful endpoint in the era of immunotherapy?

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sukhvinder Johal ◽  
Irene Santi ◽  
Justin Doan ◽  
Saby George
Keyword(s):  
Overall Survival ◽  
Disease Progression ◽  
Tumor Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Apparent Lack ◽  
Free Survival ◽  
Treatment Beyond Progression ◽  
Significant Difference

488 Background: Progression-free survival (PFS) is often used as a primary endpoint in oncology clinical trials as a surrogate for overall survival. Traditionally, the Response Evaluation Criteria in Solid Tumors (RECIST) have defined disease progression as a significant increase in the size of tumor lesions and the development of new lesions. However, some patients starting immunotherapy have shown initial increased size of tumor lesions followed by tumor regression, due to the unique mechanism of action of immunotherapies. This initial “pseudo-progression” could be classified inaccurately as disease progression, as evidenced by benefit from the treatment beyond progression approach ( JAMA Oncol 2016). The phase III CheckMate 025 trial of nivolumab versus everolimus in patients with advanced renal cell carcinoma allowed treatment beyond progression if there was investigator-assessed clinical benefit and tolerability. The purpose of our study was to test if treatment duration for an immunotherapy was different from RECIST-defined PFS, and as such, could potentially explain the apparent lack of correlation between RECIST progression and overall survival shown in CheckMate 025. Methods: Using 1-year data from CheckMate 025, Kaplan–Meier methodology was used to estimate the median duration of PFS and time to treatment discontinuation (TTD). Stratified log-rank test was used to assess the difference in treatments. Results: For all patients, the median PFS with nivolumab was 4.6 months (95% CI, 3.7–5.4 months) and median TTD was 6.2 months (95% CI, 5.6–7.7 months). For everolimus, the median PFS was 4.4 months (95% CI, 3.7–5.5 months) and median TTD was 3.9 months (95% CI, 3.7–4.6 months). Conclusions: Patients in CheckMate 025 had significantly longer survival with nivolumab than with everolimus, but with similar PFS. Our analysis demonstrated that while PFS was similar to TTD with everolimus, there was a significant difference between the 2 measures for nivolumab, suggesting that RECIST-defined PFS may not be the proper endpoint to define progression for immunotherapies. Further evaluation of the association of TTD and other immune-related progression endpoints with overall survival is warranted. Clinical trial information: NCT01668784.

Association of early tumor shrinkage with progression-free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 749-749
Author(s):  
Hiroshi Nakatsumi ◽  
Satoshi Yuki ◽  
Tetsuhito Muranaka ◽  
Hiraku Fukushima ◽  
Takashi Kato ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Tumor Shrinkage ◽  
First Line ◽  
Free Survival ◽  
Log Rank Test ◽  
Early Tumor Shrinkage ◽  
Significant Difference ◽  
Early Tumor

749 Background: It was reported that early tumor shrinkage (ETS) was associated with better overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) receiving cetuximab. We investigated association of ETS with progression free survival (PFS) in pts with unresectable colorectal liver metastases (CLM) from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety and so on. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. In this analysis, association of ETS at 8 weeks from the start of chemotherapy with pts characteristics, PFS and TTF was evaluated. Pts characteristics were compared using Student-t test, chi-square test and Fisher’s exact test. PFS and TTF were analyzed with Kaplan-Meier method and compared using log-rank test. Univariate analysis for the association of pts characteristics with PFS and TTF was performed using log-rank test, and multivariate analysis was performed using Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 74 pts with CLM were evaluable for ETS. Forty-nine pts (66.2%) had ETS ≥20%. The pts characteristics between ETS ≥20% and <20% were well balanced. The median PFS was 7.3 months in ETS <20% versus 10.0 months in ETS ≥20% (HR 0.55; p=0.025). In multivariate analysis for PFS, there was no significant difference between ETS ≥20% and <20% (HR 0.585; p=0.066). The median TTF (ETS <20% v ≥20%) was 5,1 months vs. 7.7 months (HR 0.46; p=0.003). In multivariate analysis for TTF, there was significant difference between ETS ≥20% and <20% (HR 0.509; p=0.017). Conclusions: In this analysis, ETS ≥20% might be positive predictive marker for PFS and TTF in pts with CLM receiving first-line BV-based chemotherapy.

Timing of Second Autologous Transplantations in Multiple Myeloma: Results of a Multicenter Sequential Randomized Clinical Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 59-59 ◽  
Author(s):  
Abderrahman Abdelkefi ◽  
Saloua Ladeb ◽  
Tarek Ben Othman ◽  
Lamia Torjman ◽  
Amel Lakhal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Rank Test ◽  
Optimal Timing ◽  
High Dose ◽  
Consolidation Therapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Log Rank Test

Abstract Background: Autologous stem cell transplantation (ASCT) is now considered standard therapy in young patients (<65 years) with multiple myeloma (MM). The Intergroupe Francophone du Myelome conducted a randomized trial of the treatment of MM with high-dose chemotherapy followed by either one or two successive ASCTs. The probabilities of event-free-survival and overall survival were doubled with a double transplant. However, no randomized trial has compared tandem transplant up-front with a strategy including planned second ASCT at relapse or progression. Therefore, we performed a multicenter, sequential, randomized trial designed to assess the optimal timing of a second ASCT. Methods: From May 2003 to April 2006, 140 patients with symptomatic MM (de novo) and less than 60 years of age, were randomly assigned to receive either tandem transplantation up-front (within 6 months of the first transplantation) [Arm A, n=69] or one ASCT followed by a consolidation therapy with thalidomide (day +90, 100 mg/per day during 5 months) [Arm B, n=71]. Patients included in the arm B received a second transplant in case of disease progression on consolidation therapy, or in case of relapse in responders. Clinical characteristics of each group were similar. In both arms of the study, ASCT was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m2) and G-CSF. Data were analyzed on an intent-to-treat basis. Results: With a median follow-up of 23 months (range: 6–34), the 2-year overall survival was 55% in the arm A and 75% in the arm B. Survival curves were not different (P=0.28, log-rank test). The 2-year event-free survival was 41% in the arm A and 60% in the arm B (P=0.4, log-rank-test). In the arm B, relapse-free survival of ≥ 16 months following the first transplantation was an important predictor of overall survival (p< 0.001). Conclusion: Data from the present study suggest that up-front single ASCT followed by a consolidation therapy with thalidomide and a second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients. Longer follow-up is needed before definite conclusions can be given concerning the optimal timing of second autologous transplantations in patients with MM.

scholarly journals Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial

2019 ◽  
Vol 37 (34) ◽  
pp. 3223-3233 ◽  
Author(s):  
Yanhong Deng ◽  
Pan Chi ◽  
Ping Lan ◽  
Lei Wang ◽  
Weiqing Chen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
Chinese Patients ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

scholarly journals Relationship Between Postoperative Lordosis Distribution Index And Adjacent Segment Disease Following L4-S1 Posterior Lumbar Interbody Fusion

2020 ◽  
Author(s):  
Guoquan Zheng ◽  
Chunguo Wang ◽  
Tianhao Wang ◽  
Wenhao Hu ◽  
Quanbo Ji ◽  
...  
Keyword(s):  
Lumbar Lordosis ◽  
Rank Test ◽  
Adjacent Segment ◽  
Free Survival ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Distribution Index ◽  
Lower Lumbar ◽  
The Impact

Abstract Background. ASD is an acknowledged problem of PLIF. Many studies have been reported concerning the role of LDI in spinal biomechanics. However, few reports have been published about the impact of LDI on ASD following L4-S1 PLIF. Methods. The study enrolled 200 subjects who underwent L4-S1 PLIF for degenerative spine disease from 2009 to 2014. The average follow-up term was 84 months. Several lower lumbar parameters were measured, including lower lumbar lordosis (LLL), lumbar lordosis (LL) and LDI on the pre- and postoperative radiograph. Perioperative information, comorbidities and operative data were documented. Kaplan-Meier curves were plotted for the comparisons of ASD-free survival of 3 different kinds of postoperative LDI subgroups. Results. The incidence of ASD was found to be 8.5%. LL and LLL increased by 3.96 ° (38.71 ° vs 42.67 ° , P ＜ 0.001) and 3.60 ° (26.22 ° vs 28.82 ° , P ＜ 0.001) after lower lumbar fusion surgery, respectively. Lordosis distribution index (LDI) increased by 0.03 (0.66 vs 0.69, P=0.004) postoperatively. A significant difference(P=0.001) was observed when comparing the incidence of ASD among postoperative LDI subgroups. The Kaplan-Meier curves showed a marked difference in ASD-free survival between low and moderate LDI subgroup (Log Rank test, P=0.0012) , high and moderate LDI subgroup (Log Rank test, P=0.0005) Conclusion. Patients with abnormal postoperative LDI were statistically more likely to develop ASD than those who had normal postoperative LDI. Moreover, patients with low postoperative LDI were at greater risk for developing ASD than those with high postoperative LDI over time.

scholarly journals Phase III Trial of Carboplatin and Paclitaxel With or Without Sorafenib in Metastatic Melanoma

2013 ◽  
Vol 31 (3) ◽  
pp. 373-379 ◽  
Author(s):  
Keith T. Flaherty ◽  
Sandra J. Lee ◽  
Fengmin Zhao ◽  
Lynn M. Schuchter ◽  
Lawrence Flaherty ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
End Points ◽  
Free Survival ◽  
Log Rank Test ◽  
The Difference

Purpose The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma. Patients and Methods In this double-blind, randomized, placebo-controlled phase III study, all patients received carboplatin at area under the [concentration-time] curve 6 and paclitaxel 225 mg/m2 intravenously once every 21 days with random assignment to sorafenib 400 mg orally twice per day on days 2 through 19 every 21 days or placebo. The primary end point was OS, and secondary end points included progression-free survival, objective tumor response, and toxicity. Results In all, 823 patients were enrolled over 34 months. At final analysis, the median OS was 11.3 months (95% CI, 9.8 to 12.2 months) for CP and 11.1 months (95% CI, 10.3 to 12.3 months) for CPS; the difference in the OS distribution was not statistically significant by the stratified log-rank test, stratified on American Joint Committee on Cancer (AJCC) stage, Eastern Cooperative Oncology Group (ECOG) performance status, and prior therapy (P = .878). Median progression-free survival was 4.9 months for CPS and 4.2 months for CP (P = .092, stratified log-rank test). Response rate was 20% for CPS and 18% for CP (P = .427). More patients on the CPS arm had grade 3 or higher toxicities (84% v 78%; P = .027), with increased rash, hand-foot syndrome, and thrombocytopenia accounting for most of the difference. Conclusion Sorafenib does not improve OS when given in combination with CP for chemotherapy-naive patients with metastatic melanoma. This study establishes benchmark end points for the CP regimen in first-line therapy of metastatic melanoma.

Post-Consolidation Immunotherapy with Histamine Dihydrochloride and Interleukin-2 in AML: Long Term Follow-Up of Leukemia-Free Survival and Overall Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1846-1846 ◽  
Author(s):  
Mats L. Brune ◽  
Jacob M. Rowe ◽  
Jeff Szer ◽  
Donna E. Hogge ◽  
John Catalano ◽  
...  
Keyword(s):  
Overall Survival ◽  
Interleukin 2 ◽  
Phase Iii ◽  
Histamine Dihydrochloride ◽  
Free Survival ◽  
Treatment Groups ◽  
Treatment Standard ◽  
Phase Iii Study

Abstract PURPOSE. To assess the long-term outcome of AML patients (pts) in complete remission (CR) after a phase III study which compared the effect of post-consolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) on leukemia-free survival (LFS) and overall survival (OS). PATIENTS & METHODS. A multi-national, randomized, open-label, phase III study which recruited 261 AML pts in first remission (CR1) and 59 in subsequent remission (CR&gt;1) was conducted between June 1998 and October 2000. Pts were enrolled after after termination of consolidation therapy, stratified by country and CR status, and randomized to either treatment or no treatment (standard of care, control). Forty-one % of pts were &gt;60 yrs (median 57), and 54% were males. Study arms were balanced for known prognostic factors. Two patient populations were studied, i.e. all pts randomized (ITT population; n=320) and pts in CR1. The treatment was self-administered at home and included ten 3-week courses of low-dose IL-2 (aldesleukin, Chiron Corp) 18 000 U/kg sc bid, plus HDC (EpiCept) 0.5 mg sc bid. Cycles 1–3 comprised 3 wks of treatment and 3 wks of rest, whereas in cycles 4–10 the rest periods were 6 wks. As reported previously (Blood2006; 108:88), the trial met the primary endpoint of prolonged leukemia-free survival (LFS) for all pts randomized (p=0.008 in favor of the treatment arm) at a median of 46 months of follow-up. The present long-term assessment of efficacy was conducted in August 2006, 30 months after the lock of the original data base. RESULTS. Follow-up forms were retrieved from 86% (n=107; 59 HDC/IL-2 recipients, 48 no treatment,) of the 124 pts pts who were alive at original study cut-off. In the long-term analysis, median LFS in the ITT population was 11 and 8.8 months in HDC/IL-2 and no treatment groups, respectively. In the CR1 population, median LFS was 15 and 9.7 months in HDC/IL-2 and no treatment groups, respectively. The benefit of treatment both for the ITT population (p=0.017) and in CR1 pts (p=0.026) was demonstrated by log-rank testing. Kaplan-Meier (KM) estimates for LFS at 60 months revealed a trend in favor of the treatment group in the ITT population (29.6 vs 20.6%; p=0.065) and a significant difference in the CR1 population (34.4 vs 21.7%, p=0.024). The median OS of CR 1 pts were 44 months (HDC/IL-2) and 28 months (no treatment), but the difference did not attain statistical significance (log rank test: p=0.22; KM estimate at 60 months: p=0.07). CONCLUSION. Post-consolidation immunotherapy with HDC/IL-2 results in significant long-term improvement of LFS.

A randomized phase II trial of adjuvant chemotherapy with S-1 versus S-1 and gemcitabine (GS) versus gemcitabine alone (GEM) in patients with resected pancreatic cancer (CAP-002 study).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4056-4056 ◽  
Author(s):  
Hideyuki Yoshitomi ◽  
Hiroaki Shimizu ◽  
Hiroyuki Yoshidome ◽  
Masayuki Ohtsuka ◽  
Atsushi Kato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Rank Test ◽  
Free Survival ◽  
Significant Difference

4056 Background: Although the adjuvant therapy using GEM is now the standard therapy for patients with resected pancreatic cancer (PC), the prognosis still remains poor. Resent study demonstrated the non-inferiority of S-1 and superiority of GS to GEM with respect to progression free survival in patients with unresectable pancreatic cancer. Methods: Patients with invasive ductal PC who underwent radical surgery were enrolled. After stratification for R0/1, stage and institution, patients were randomized to receive GEM (GEM 1g/ m2, iv, d1, 8, and 15, q4w X12), S-1 (80/100/120mg/day based on BSA, po, d1-14, q3w X 16) or GS (S-1 60/80/100mg/day based on BSA po, d1-14 plus GEM 1g/ m2, iv, d8, 15, q3w X 16) within 8weeks after operation. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 2y disease free survival (DFS) rate and secondary endpoints included overall survival (OS), and safety. Results: Between January 2007 and October 2010, 96 patients were randomized into the three arms of the trial (32 pts to each group). Patients’ characteristics were well balanced (GEM/S-1/GS) with regard to age (66/67/66y), tumor location (head 66/69/75%), tumor status (T3+4 88/78/91%), and nodal status (positive 75/69/75%). Until November 2012, 74 events (77%) have occurred for DFS. Two year DFS rate was 24.2%, 28.1% and 34.4% in GEM, S-1 and GS, respectively and there was no significant difference between groups. The median OS was 21m in GEM, 26m in S-1 and 27.9m in GS (Log rank test: N.S.). Grade 3/4 toxicities in GEM/S-1/GS were hematological 63/10/74% and non-hematological 17/10/23%, respectively. No treatment related death was observed during the study. Conclusions: S-1 and GS provided similar efficacy to GEM as the adjuvant chemotherapy for resected PC. According to the results, S-1 and GS is the adequate combination for phase III trial to examine the efficacy of adjuvant chemotherapy for PC. Clinical trial information: UMIN000002000.

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