Efficacy and safety of bexarotene combined with psoralen/ultraviolet A light (PUVA) compared to PUVA treatment alone in stage IB-IIa mycosis fungoides (MF): Final results from EORTC cutaneous lymphoma task force (CLTF) phase III clinical trial 21011.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8076-8076
Author(s):  
Sean Whittaker ◽  
Pablo L. Ortiz-Romero ◽  
Reinhard Dummer ◽  
Annamari Ranki ◽  
Baktiar Hasan ◽  
...  
Keyword(s):  
Task Force ◽  
Statistical Significance ◽  
Median Number ◽  
Phase Iii ◽  
P Value ◽  
Open Label ◽  
Stage Ib ◽  
Treatment Standard ◽  
Significant Difference ◽  
Grade 3

8076 Background: Skin-directed treatment with methoxsalen (PUVA) is the current treatment standard in stage IB-IIA MF. A combination of PUVA and bexarotene might be of additional clinical benefit for MF stage I/II patients (pts). Methods: EORTC 21011 was a randomised, open label phase III study comparing combined bexarotene and PUVA versus PUVA alone in pts with stage IB and IIA MF. Study primary endpoint was response (complete clinical + partial response, CCR+PR) rate; secondary endpoints: cumulative dose of UVA and number of PUVA sessions necessary to achieve a CCR, duration of CCR, time to relapse, safety and percentage of drop-outs. Results: The study recruited stage IB/IIA MF pts and was prematurely closed due to low accrual after 93/145 required pts (65%) were randomized; 45 to PUVA, 48 to PUVA+bexarotene. Median number of PUVA weeks were 12 (1-17) in PUVA vs. 10.5 (1-16) in combination arm. Total UVA doses were 107J/cm2 (1.4-489.9) in PUVA vs. 101.7J/cm2 (0.2-529.9) in combination arm. Few grade 3-4 toxicities were observed in both arms (liver enzyme elevation, neutropenia, anemia, increased cholesterol, photosensitivity, pruritus, rash, hypertriglyceridemia). Best overall response (CCR/PR) rate was 71.1% (33/45) for PUVA alone and 77.1% (37/48) for combination arm (p-value=0.57). The median of duration of response was 9.6 for PUVA vs 5.8 months for combination arm (p value=0.33). CCR was seen in 25 pts, 10 in PUVA (CCR 24%) and 15 in combination therapy (CCR 33%) (pvalue=0.45). Similarily, a lower UVA dose was required to achieve a CCR in the combination arm (median of 55.8 J/cm2) compared to the PUVA arm (median of 117.58 J/cm2) (p value=0.5). Conclusions: No significant difference in response rate was observed in this study. There was a trend towards fewer PUVA sessions and lower UVA dose to achieve CCR in the PUVA/bexarotene combination arm (median of 27.5 vs. 22,p-value = 0.11) but this did not achieve statistical significance due to insufficient power. The safety profile was acceptable, as there were only few grade 3-4 toxicities observed in both arms.

Phase III study of tislelizumab plus chemotherapy vs chemotherapy alone as first-line (1L) treatment for advanced squamous non-small cell lung cancer (sq NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9554-9554
Author(s):  
Jie Wang ◽  
Xinmin Yu ◽  
Shun Lu ◽  
Yanping Hu ◽  
Yuping Sun ◽  
...  
Keyword(s):  
Tumor Stage ◽  
Median Number ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Open Label ◽  
Open Label Phase ◽  
Independent Review ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Number Of Treatment

9554 Background: Tislelizumab is an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis. Tislelizumab in combination with chemotherapy has demonstrated a manageable tolerability profile and preliminary efficacy as 1L treatment for NSCLC. Methods: In this open-label phase 3 study (NCT03594747), Chinese pts with histologically confirmed stage IIIB or IV sq NSCLC were randomized (1:1:1) to receive IV Q3W: tislelizumab (200 mg, D1) + paclitaxel (P; 175 mg/m2, D1) and carboplatin (carb; AUC 5, D1) ( Arm A); tislelizumab + nab-P (100 mg/m2; D1, 8, and 15) and carb (AUC 5, D1) ( Arm B); or P (175 mg/m2, D1) and carb (AUC 5, D1) ( Arm C). Chemotherapy was administered for 4-6 cycles followed by tislelizumab. Patients were stratified by tumor stage and PD-L1 expression. The primary endpoint, PFS per RECIST v1.1, was assessed by Independent Review Committee; key secondary endpoints included OS, ORR, DoR, and safety/tolerability. Results: Across 360 pts, median PFS was significantly improved with tislelizumab plus chemotherapy ( Arms A and B) compared with chemotherapy alone ( Arm C) (Table). As of 6 Dec 2019, ORRs were higher and median DoRs were longer in Arms A and B vs Arm C. Across all arms, median OS was not reached and median number of treatment cycles were comparable. Adverse events (AEs) leading to discontinuation of any treatment were reported in 12.5%, 29.7%, and 15.4% of pts in Arms A, B, and C, respectively. The most commonly reported grade ≥3 AEs were hematologic in nature (eg, neutropenia) and consistent with known chemotherapy AEs. Serious treatment-related AEs (TRAEs) were reported in 72 pts (37.5% [ A]; 38.9% [ B]; 23.6% [ C]); TRAEs leading to death were reported in 6 pts (n=1 [ A]; n=2 [ B]; n=3 [ C]), none of which were solely attributed to tislelizumab. Conclusions: As 1L treatment for advanced sq NSCLC, addition of tislelizumab to P/carb or nab-P/carb chemotherapy significantly improved PFS and showed higher ORR and longer DoR than chemotherapy alone. The safety profile is in line with the known profiles of tislelizumab, chemotherapy, and underlying NSCLC; no new safety signals were identified with addition of tislelizumab to chemotherapy. Clinical trial information: NCT03594747 . [Table: see text]

A randomized phase III trial of S-1/oxaliplatin (SOX) plus bevacizumab versus 5-FU/l-LV/oxaliplatin (mFOLFOX6) plus bevacizmab in patients with metastatic colorectal cancer: The SOFT study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3519-3519 ◽  
Author(s):  
Daisuke Takahari ◽  
Yasuhide Yamada ◽  
Hiroshi Matsumoto ◽  
Hideo Baba ◽  
Kazuhiro Yoshida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
P Value ◽  
Open Label ◽  
Phase Iii Trial ◽  
Open Label Phase ◽  
Grade 3 ◽  
Ecog Ps

3519 Background: Several studies of oxaliplatin plus S-1 combination therapy (SOX) conducted in Asia have shown promising efficacy and safety for metastatic colorectal cancer (mCRC), suggesting the potential to replace mFOLFOX6. We performed a randomized phase III trial to determine whether SOX plus bevacizmab (SOX+Bev) is non-inferior to mFOLFOX6 plus bevacizmab (mFOLFOX6+Bev) in terms of progression-free survival (PFS). Methods: The SOFT study was a randomized, open-label, phase III trial. Chemotherapy-naïve patients (pts) with mCRC, an ECOG PS of 0-1, and adequate organ functions were randomized to receive either mFOLFOX6+Bev (5 mg/kg of bevacizumab, followed by 200 mg/m2 of l-leucovorin given simultaneously with 85 mg/m2 of oxaliplatin, followed by a 400 mg/m2 bolus of 5-FU on day 1 and then 2,400 mg/m2 of 5-FU over 46 h, every 2 weeks) or SOX+Bev (7.5 mg/kg of bevacizumab, 130 mg/m2 of oxaliplatin on day 1, and 40−60 mg of S-1 twice daily for 2 weeks, followed by a 1-week rest). The primary endpoint was PFS. A sample size of 225 pts per group was estimated to be necessary based on a median PFS of 10.0 months in each group and an 80% power to demonstrate non-inferiority of SOX+Bev with a 2.5-month margin (hazard ratio, HR = 1.33) and a 2-sided alpha of 0.05. Results: A total of 512 pts were enrolled from February 2009 to March 2011. Data were analyzed after confirming >388 events as planned. Demographic factors were well balanced. Pts received a median of 12 cycles (1 cycle = 2 weeks) of mFOLFOX6+Bev and 8 cycles (1 cycle = 3 weeks) of SOX+Bev (range: 1−16). Median PFS was 11.5 months (95% CI: 10.7−13.2) with mFOLFOX6+Bev and 11.7 months (95% CI: 10.7−12.9) with SOX+Bev. The adjusted HR for PFS was 1.043 (95% CI: 0.860−1.266), and the p value for non-inferiority was 0.0139. Response rate was 62.7% with mFOLFOX6+Bev and 61.5% with SOX+Bev. Grade 3/4 toxicities (%) with mFOLFOX6+Bev/SOX+Bev were leukopenia 8.4/2.4, neutropenia 33.7/8.8, anorexia 1.2/5.2, and diarrhea 2.8/9.2. Conclusions: SOX+Bev is non-inferior to mFOLFOX6+Bev with respect to PFS as 1st-line treatment for mCRC and thus can replace mFOLFOX6+Bev. Clinical trial information: JapicCTI-090699.

Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): Updated results from the phase III CASPIAN study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9002-9002 ◽  
Author(s):  
Luis G. Paz-Ares ◽  
Mikhail Dvorkin ◽  
Yuanbin Chen ◽  
Niels Reinmuth ◽  
Katsuyuki Hotta ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Standard Of Care ◽  
Analysis Data ◽  
Phase Iii ◽  
Open Label ◽  
Primary Endpoints ◽  
Open Label Phase ◽  
First Results ◽  
Treatment Naïve ◽  
Grade 3

9002 Background: CASPIAN is an open-label, Phase 3 study of durvalumab (D) ± tremelimumab (T) + etoposide and either cisplatin or carboplatin (EP) for pts with 1L ES-SCLC. At the planned interim analysis (data cutoff Mar 11, 2019; 63% maturity), D + EP demonstrated a statistically significant improvement in OS compared with EP alone (HR 0.73 [95% CI 0.59–0.91]; p=0.0047). Here we present a planned updated analysis of OS for D + EP vs EP and the first results for D + T + EP vs EP. Methods: Treatment-naïve pts with ES-SCLC (WHO PS 0/1) were randomized 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. In the IO arms, pts received 4 cycles of EP + D ± T, followed by maintenance D 1500 mg q4w until disease progression. Pts received one additional dose of T 75 mg post EP in the D + T + EP arm. In the EP arm, pts received up to 6 cycles of EP and optional PCI (investigator’s discretion). The two primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP. Results: 268, 268 and 269 pts were randomized to D + EP, D + T + EP and EP, respectively; baseline characteristics were generally well balanced across arms. As of Jan 27, 2020, the median follow-up was 25.1 mo, 82% maturity. D + EP continued to demonstrate improvement in OS vs EP, with a HR of 0.75 (95% CI 0.62–0.91; nominal p=0.0032); median OS 12.9 vs 10.5 mo, respectively. 22.2% of pts were alive at 2 y with D + EP vs 14.4% of pts with EP. D + T + EP numerically improved OS vs EP, however this did not reach statistical significance per the prespecified statistical plan: HR 0.82 (95% CI 0.68–1.00; p=0.0451 [p≤0.0418 required for stat sig]); the median OS was 10.4 mo and 23.4% of pts were alive at 2 y. Secondary endpoints of PFS and ORR remained improved with D + EP vs EP and will be presented. Confirmed investigator-assessed ORR was similar for D + T + EP vs EP (58.4% vs 58.0%). Median PFS was similar for D + T + EP vs EP (4.9 mo vs 5.4 mo), but the 12-mo PFS rate was numerically higher (16.9% vs 5.3%); PFS HR 0.84 (95% CI 0.70–1.01). In the D + EP, D + T + EP and EP arms, respectively, incidences of all-cause AEs of Grade 3/4 were 62.3%, 70.3% and 62.8%; AEs leading to discontinuation 10.2%, 21.4% and 9.4%; and AEs leading to death 4.9%, 10.2% and 5.6%. Conclusions: The addition of durvalumab to EP continued to demonstrate improvement in OS compared with a robust control arm, further supporting this regimen as a new standard of care for 1L ES-SCLC offering the flexibility of platinum choice. No additional benefit was observed when T was combined with D + EP in this pt population. Safety findings in all arms remained consistent with the known safety profiles of all agents. Clinical trial information: NCT03043872.

Exploratory analyses of efficacy and safety of pemetrexed (Pem) plus bevacizumab (Bev) and bev alone as maintenance therapy (MT) in patients (Pts) with stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8012-8012
Author(s):  
Jyoti D. Patel ◽  
Edward B. Garon ◽  
Ramaswamy Govindan ◽  
Craig H. Reynolds ◽  
David R. Spigel ◽  
...  
Keyword(s):  
Survival Rates ◽  
Sensory Neuropathy ◽  
Median Number ◽  
Stage Iiib ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase ◽  
The Difference ◽  
Grade 3

8012 Background: In a phase III superiority study, Pem+carboplatin (Cb)+Bev followed by Pem+Bev improved PFS compared with paclitaxel (Pac)+Cb+Bev followed by Bev in NS-NSCLC pts. Superior OS (primary endpoint) was not met. These analyses assessed the efficacy and safety in pts who received MT. Methods: Prespecified exploratory analyses were performed in the maintenance population (MP) and timed from the start of induction. Pts ≥18 years with stage IIIB/IV NS-NSCLC (ECOG status 0–1) from the multicenter, randomized, open-label, phase III superiority study were included in the MP if they received at least one dose of MT. For MT, pts received intravenous Pem 500 mg/m2+Bev 15 mg/kg (n=292) or Bev 15 mg/kg (n=298). OS, PFS, and safety were evaluated. Comparison is made to the intent-to-treat (ITT; Pem=472, Pac=467) or safety population (SP; Pem=442, Pac=443; received at least one dose of one drug). Results: Baseline pt and disease characteristics for the ITT and MP were similar between arms. In the ITT/MP population, the median number of cycles was 7/10 (range, 1-41/4–41) in the Pem arm and 6/9 (range, 1-39/5–39) in the Pac arm. In the ITT/MP, OS was 12.6/17.7 months (mos; Pem) and 13.4/15.7 mos (Pac). Survival rates (%) at 12 and 24 mos with Pem (ITT/MP) were 52.7/71.7 and 24.4/34.5; Pac, 54.1/66.5 and 21.2/26.5%. In pts not receiving MT, OS was 4.7 mos (Pem) and 6.1 mos (Pac). PFS (mos) in the ITT/MT was 6.0/8.6 (Pem) and 5.6/6.9 (Pac). In pts not receiving MT, PFS was 2.3 mos and 2.5 mos with Pem and Pac, respectively. From induction, both SP/MP had significantly more grade 3/4 thrombocytopenia, anemia, and fatigue with Pem and neutropenia and sensory neuropathy with Pac (p≤0.001). During MT only, the difference in grade 3/4 neutropenia rates between arms was no longer significant. Conclusions: Improved efficacy outcomes were consistent with previous Pem maintenance and Bev studies and no new toxicities were observed. Clinical trial information: NCT00762034.

SOPHIA analysis by chemotherapy (Ctx) choice: A phase III (P3) study of margetuximab (M) + Ctx versus trastuzumab (T) + Ctx in patients (pts) with pretreated HER2+ metastatic (met) breast cancer (MBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1040-1040 ◽  
Author(s):  
Santiago Escrivá ◽  
Seock-Ah Im ◽  
Fatima Cardoso ◽  
Javier Cortes ◽  
Giuseppe Curigliano ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Phase Iii ◽  
Rank Test ◽  
Test Results ◽  
Open Label ◽  
Innate And Adaptive Immunity ◽  
Antiproliferative Effects ◽  
Primary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

1040 Background: Despite advances, pretreated HER2+ MBC remains incurable with ongoing need for new therapies. Investigational M has similar HER2 binding and antiproliferative effects as T. Relative to T, M Fc engineering increases binding affinity for both variants of activating Fc receptor (FcR) CD16A and decreases affinity for inhibitory FcR CD32B, coordinately activating innate and adaptive immunity. In a Phase 3 (P3) trial, M prolonged PFS over T (Table). Second interim OS results from Sept 2019 also favor M (hazard ratio [HR], 0.89; 95% CI 0.69–1.13; nominal P=0.326). Methods: SOPHIA (NCT02492711), an open-label P3 trial, enrolled pts with HER2+ MBC after pertuzumab and 1–3 lines of prior treatment (Tx) for MBC. Randomization was 1:1 to M (15 mg/kg IV q3w + Ctx) or T (6 [8 for loading dose] mg/kg IV q3w + Ctx), stratified by met sites (≤2, >2), lines of Tx for met disease (≤2, >2), and Ctx choice, including capecitabine (Cap), eribulin (Eri), gemcitabine (Gem), or vinorelbine (Vin). Primary endpoints were central blinded PFS and OS, assessed sequentially using the stratified log-rank test. Results: Investigator chemotherapy choices and results by chemotherapy are shown in the table. Subjects receiving Eri and Gem had the lowest PFS hazards ratios (HRs), favoring M over T, although no statistical significance of individual chemotherapy subgroups was seen. There was variable toxicity among Ctx subgroups, and fewer subjects receiving Cap had Ctx related Grade 3 or higher (>=Gr 3) AEs. In this unblinded study, more subjects on M than T in all subgroups discontinued Ctx while continuing study antibody. Conclusions: In combination with chemotherapy in pretreated HER2+ MBC, M improved PFS over T. Safety was manageable in all Ctx subgroups. Differences among HRs for chemotherapy subgroups may be driven by selection bias and/or sensitivity differences. Clinical trial information: NCT02492711 . [Table: see text]

scholarly journals Plectranthus amboinicusandCentella asiaticaCream for the Treatment of Diabetic Foot Ulcers

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yuan-Sung Kuo ◽  
Hsiung-Fei Chien ◽  
William Lu
Keyword(s):  
Diabetic Foot ◽  
Statistical Significance ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Open Label ◽  
Safe Alternative ◽  
Significant Difference ◽  
Grade 3

Effects of a topical cream containingP. amboinicus(Lour.) Spreng. (Lamiaceae) andC. asiatica(L.) Urban (Umbelliferae) were evaluated and compared to effects of hydrocolloid fiber wound dressing for diabetic foot ulcers. A single-center, randomized, controlled, open-label study was conducted. Twenty-four type 1 or type 2 diabetes patients aged 20 years or older with Wagner grade 3 foot ulcers postsurgical debridement were enrolled between October 2008 and December 2009. Twelve randomly assigned patients were treated with WH-1 cream containingP. amboinicusandC. asiaticatwice daily for two weeks. Another 12 patients were treated with hydrocolloid fiber dressings changed at 7 days or when clinically indicated. Wound condition and safety were assessed at days 7 and 14 and results were compared between groups. No statistically significant differences were seen in percent changes in wound size at 7- and 14-day assessments of WH-1 cream and hydrocolloid dressing groups. A slightly higher proportion of patients in the WH-1 cream group (10 of 12; 90.9%) showed Wagner grade improvement compared to the hydrocolloid fiber dressing group but without statistical significance. For treating diabetic foot ulcers,P. amboinicusandC. asiaticacream is a safe alternative to hydrocolloid fiber dressing without significant difference in effectiveness.

Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Progressive or Recurrent Ovarian Cancer

2008 ◽  
Vol 26 (6) ◽  
pp. 890-896 ◽  
Author(s):  
Gabriella Ferrandina ◽  
Manuela Ludovisi ◽  
Domenica Lorusso ◽  
Sandro Pignata ◽  
Enrico Breda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Liposomal Doxorubicin ◽  
Statistical Significance ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Primary Treatment ◽  
Phase Iii ◽  
Significant Difference ◽  
Grade 3

Purpose We aimed at investigating the efficacy, tolerability, and quality of life (QOL) of gemcitabine (GEM) compared with pegylated liposomal doxorubicin (PLD) in the salvage treatment of recurrent ovarian cancer. Patients and Methods A phase III randomized multicenter trial was planned to compare GEM (1,000 mg/m2 on days 1, 8, and 15 every 28 days) with PLD (40 mg/m2 every 28 days) in ovarian cancer patients who experienced treatment failure with only one platinum/paclitaxel regimen and who experienced recurrence or progression within 12 months after completion of primary treatment. Results One hundred fifty-three patients were randomly assigned to PLD (n = 76) or GEM (n = 77). Treatment arms were well balanced for clinicopathologic characteristics. Grade 3 or 4 neutropenia was more frequent in GEM-treated patients versus PLD-treated patients (P = .007). Grade 3 or 4 palmar-plantar erythrodysesthesia was documented in a higher proportion of PLD patients (6%) versus GEM patients (0%; P = .061). The overall response rate was 16% in the PLD arm compared with 29% in the GEM arm (P = .056). No statistically significant difference in time to progression (TTP) curves according to treatment allocation was documented (P = .411). However, a trend for more favorable overall survival was documented in the PLD arm compared with the GEM arm, although the P value was of borderline statistical significance (P = .048). Statistically significantly higher global QOL scores were found in PLD-treated patients at the first and second postbaseline QOL assessments. Conclusion GEM does not provide an advantage compared with PLD in terms of TTP in ovarian cancer patients who experience recurrence within 12 months after primary treatment but should be considered in the spectrum of drugs to be possibly used in the salvage setting.

Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study

2019 ◽  
Vol 37 (8) ◽  
pp. 658-667 ◽  
Author(s):  
Julien Edeline ◽  
Meher Benabdelghani ◽  
Aurélie Bertaut ◽  
Jérôme Watelet ◽  
Pascal Hammel ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
Open Label ◽  
Tract Cancer ◽  
R1 Resection ◽  
Significant Difference ◽  
Related Quality ◽  
Health Related ◽  
Grade 3

PURPOSE No standard adjuvant treatment currently is recommended in localized biliary tract cancer (BTC) after surgical resection. We aimed to assess whether gemcitabine and oxaliplatin chemotherapy (GEMOX) would increase relapse-free survival (RFS) while maintaining health-related quality of life (HRQOL) in patients who undergo resection. PATIENTS AND METHODS We performed a multicenter, open-label, randomized phase III trial in 33 centers. Patients were randomly assigned (1:1) within 3 months after R0 or R1 resection of a localized BTC to receive either GEMOX (gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 infused on day 2 of a 2-week cycle) for 12 cycles (experimental arm A) or surveillance (standard arm B). Primary end points were RFS and HRQOL. RESULTS Between July 2009 and February 2014, 196 patients were included. Baseline characteristics were balanced between the two arms. After a median follow-up of 46.5 months (95% CI, 42.6 to 49.3 months), 126 RFS events and 82 deaths were recorded. There was no significant difference in RFS between the two arms (median, 30.4 months in arm A v 18.5 months in arm B; hazard ratio [HR], 0.88; 95% CI, 0.62 to 1.25; P = .48). There was no difference in time to definitive deterioration of global HRQOL (median, 31.8 months in arm A v 32.1 months in arm B; HR, 1.28; 95% CI, 0.73 to 2.26; log-rank P = .39). Overall survival was not different (median, 75.8 months in arm A v 50.8 months in arm B; HR, 1.08; 95% CI, 0.70 to 1.66; log-rank P = .74). Maximal adverse events were grade 3 in 62% (arm A) versus 18% (arm B) and grade 4 in 11% versus 3% ( P < .001). CONCLUSION There was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.

Randomized Phase III Trial of Sequential Adjuvant Chemoradiotherapy With or Without Erythropoietin Alfa in Patients With High-Risk Cervical Cancer: Results of the NOGGO-AGO Intergroup Study

2011 ◽  
Vol 29 (28) ◽  
pp. 3791-3797 ◽  
Author(s):  
Jens-Uwe Blohmer ◽  
Stefan Paepke ◽  
Jalid Sehouli ◽  
Dirk Boehmer ◽  
Martin Kolben ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Iii ◽  
Adjuvant Chemoradiotherapy ◽  
Pelvic Radiotherapy ◽  
Open Label ◽  
Phase Iii Trial ◽  
Stage Ib ◽  
Significant Difference ◽  
Phase Iii Study ◽  
Erythropoietin Alfa

Purpose This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy. Patients and Methods Two hundred fifty-seven patients were randomly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free survival (RFS). Secondary end points included overall survival (OS), change in hemoglobin levels, and safety, including thromboembolic events. Results The estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for patients receiving CRT. There was no statistically significant difference in RFS, although a trend favoring patients treated with CRT + EPO was observed (hazard ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR, 0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR, 0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88; 95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained higher hemoglobin levels throughout CRT. No significant differences in safety profiles were observed between the two groups. Incidence of thrombovascular events was low (2%) and comparable between both groups. Conclusion This study confirms that EPO can be added safely to CRT in patients with cervical cancer, but it failed to demonstrate a significant benefit in RFS and OS.

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