A multicenter exploratory study of irinotecan-based chemotherapy on UGT1A1 polymorphisms for patients with colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 563-563
Author(s):  
Motoya Chikakiyo ◽  
Hirohiko Sato ◽  
Nobuhiro Kurita ◽  
Takashi Iwata ◽  
Kozo Yoshikawa ◽  
...  
Keyword(s):  
Response Rate ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Complete Response ◽  
Uridine Diphosphate ◽  
Second Line ◽  
Wild Type ◽  
Type Group ◽  
Significant Difference ◽  
In The Wild

563 Background: Recent pharmacogenetic studies have revealed a significant association between uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6 and toxicities such as severe diarrhea and neutropenia under treatment with irinotecan. Moreover, the latter of these two polymorphisms is specifically detected in East Asian populations. We performed a prospective study to determine the optimal dose of this drug depending on which polymorphism is present in order to maximize the effectiveness of therapy while avoiding side effects. Methods: 59 patients from 11 institutions were enrolled in this study. Patients were assigned to one of the following three groups: wild type (*1/*1), heterozygous (*28/*1, *6/*1), or homozygous (*28/*28, *6/*6*, *28/*6*). The double heterozygous state (*28/*6) was included within the homozygous group. Second-line FOLFIRI was administered, with the dose of irinotecan at 150 mg/m2, in the wild type and heterozygous groups and at 100 mg/m2 in the homozygous group. The incidences of severe toxicities according to UGT1A1 gene type, response rate, and progression-free survival were investigated. Results: 26 (44.1%) were assigned to the wild type group, 28 (47.4%) to the heterozygous group, and 5 (8.5%) to the homozygous group. Grade 3 or higher severe toxicities were observed in 8 patients (30.8%) in the wild type group, 5 (17.9%) in the heterozygous group, and 1 (20.0%) in the homozygous group. No significant difference was observed among the three groups. The most frequently observed severe toxicities were neutropenia, nausea, vomiting, and diarrhea. The overall response rate (complete response + partial response) was 2 patients (7.7%) in the wild type group, 2 (7.1%) in the heterozygous group, and none (0.0%) in the homozygous group. Conclusions: In terms of tolerability and safety, the present results suggest that irinotecan should be administered at a dose of 150mg/m2 in heterozygous patients and 100 mg/m2 in homozygous patients receiving second-line FOLFIRI.

Combination of Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) for Relapsed Multiple Myeloma: Results of a Phase I/II Clinical Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 407-407 ◽  
Author(s):  
Antonio Palumbo ◽  
Maria Teresa Ambrosini ◽  
Giulia Benevolo ◽  
Patrizia Pregno ◽  
Norbert Pescosta ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Response Rate ◽  
Oral Prednisone ◽  
Progression Free Survival ◽  
Complete Response ◽  
Second Line ◽  
Open Label ◽  
Free Survival ◽  
Line Of Therapy

Abstract BACKGROUND: In newly diagnosed patients, the addition of thalidomide or bortezomib (Velcade™) to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter, open-label, non randomized, phase I/II trial, the safety/efficacy profile of the 4 drug combination, bortezomib (Velcade™), melphalan, prednisone, and thalidomide (VMPT) was evaluated in patients with relapsed/refractory myeloma. METHODS: Bortezomib was administered by IV bolus on days 1, 4, 15, 22 at three dose levels: in the first cohort (10 patients) at 1.0 mg/m2; in the second cohort (10 patients) at 1.3 mg/m2and in the third cohort (10 patients) at 1.6 mg/m2. Oral melphalan was administered at 6 mg/m2 on days 1–5, oral prednisone at 60 mg/m2 on days 1–5. Thalidomide was delivered at 50 mg on days 1–35. Each course was repeated every 35 days for a total of 6 courses. RESULTS: Thirty patients, median age 66 years (range 38–79), with relapsed or refractory myeloma were enrolled. Fourteen patients received VMPT as second line of therapy, 16 as third line. Twenty patients received prior autologous transplant, 10 conventional chemotherapy and 9 thalidomide-based regimens. After a median of 6 courses, 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good partial response (VGPR). Among patients who received VMPT as second line treatment, the PR rate was 79%, and the immunofixation negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 non-hematological adverse events included: infections (5 patients), fatigue (1), vasculitis (1) and peripheral neuropathy (2); no grade 4 toxicities were recorded. CONCLUSIONS: Initial results showed that VMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. The incidence of neurotoxicities was unexpectedly low.

scholarly journals Concurrent Chemoradiotherapy with S-1 Compared with Concurrent Chemoradiotherapy with Docetaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Significant Difference

Abstract Background: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients who had locally advanced ESCC and received CCRT with S-1 (70mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25mg/m2) and cisplatin (25mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Treatment-related toxicities, response rate, and survival outcomes were compared between groups. Results: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than in the DP group (22.2% versus 45.6%, p = 0.002). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% versus 25.0%, p = 0.275). Conclusion: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

Phase II multicenter study of second-line FOLFIRI plus cetuximab (FLIER) in patients with KRAS wild-type metastatic colorectal cancer: Final analysis of survival and additional analysis of BRAF, PI3CA mutations.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 481-481 ◽  
Author(s):  
Yasuhiro Miyake ◽  
Shigeyoshi Iwamoto ◽  
Shoichi Hazama ◽  
Fuminori Goda ◽  
Chu Matsuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Predictive Biomarker ◽  
Second Line ◽  
Wild Type ◽  
Braf Mutations

481 Background: Survival advantage of second line FOLFIRI plus cetuximab in patients with KRAS wild-type metastatic colorectal cancer has not been well reported. Since mutations in codons 12 and 13 of the KRAS gene predict lack of response to Cetuximab, mutations of V600E BRAF and PI3CA have been controversial. Methods: The aim of this study was to assess the efficacy of second-line FOLFIRI plus cetuximab in KRAS wt mCRC. Primary endpoint was response rate, other secondary endpoints were PFS, OS and safety. KRAS, BRAF, PI3CA tests by direct sequence were performed in Yamaguchi University. The starting dose of irinotecan was 150mg/ m2 (approved dose in Japan), but decreased to 100mg/m2 with UGT1A1 *28,*6 homozygous or both heterozygous. Results: From December 2008 to November 2009, 112 pts were preregistered. 67 (59.8%) pts were KRAS codon 12, 13 wt, and 60 pts were enrolled: 39 males (65%), 21 females (35%); median age was 62 years (range 37-82). The incidence of UGT1A1*28, *6 homozygous was 2.8%, 4.7% respectively. Grade 3/4 adverse events were leucopenia 26.7%, neutropenia 43.3%, paronychia 10.0%, skin toxity (fissure) 10.0% and acne 5.0%. The confirmed response rate (RECIST) was 31.7% (19/60). The median progression free survival and overall survival were 7.5 (C.I. 5.2-10.1) and 19.5 (C.I. 11.7-22.2) months respectively. Three pts had BRAF mutations and tumor shirinkage were +50.9%, +12%, +85.6% respectively. Two pts had PI3CA mutations and tumor shirinkage were +4%, +44%, respectively. Conclusions: FLIER was the first multicenter phase II trial with prospective analysis of KRAS as a predictive biomarker for cetuximab in second-line mCRC in Japan. Second-line FOLFIRI+cetuximab is well-tolerated and active. Mutations in BRAF and PI3CA gene seemed to be lack of response to cetuximab.

A phase II trial of panitumumab with irinotecan and S-1 (IRIS) as second-line treatment in patients with wild-type KRAS metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 732-732
Author(s):  
Rai Shimoyama ◽  
Tetsuo Kimura ◽  
Toshi Takaoka ◽  
Kazuki Sakamoto ◽  
Shunji Kawamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Second Line ◽  
Wild Type ◽  
Free Survival ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

732 Background: Panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in second-line chemotherapy increased objective response rate and prolonged progression-free survival (PFS) versus FOLFIRI alone in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) (Peeters et al, J Clin Oncol 2010). This trial (UMIN000004659) evaluated tolerability and efficacy of combination therapy with irinotecan and S-1, an oral fluoropyrimidine (IRIS) plus panitumumab as second-line chemotherapy in patients with WT KRASmCRC. Methods: Main inclusion criteria were: patients with WT KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/m2) and irinotecan (100 mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was completion rate of protocol therapy (CRT). The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Thirty-seven patients were enrolled in 9 centers. The overall CRT was 62.2% (23/37). Most frequent grade 3/4 toxicities were: skin rash (24%), diarrhea (16%), and appetite loss (11%). The overall RR was 32.4% (12/37). Of these, four patients underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI: 3.5-15.4 months) and 20.1 months (95% CI: 16.7-23.2 months), respectively. Conclusions: IRIS plus panitumumab has acceptable toxicity profile and promising efficacy in patients with previously treated WT KRAS mCRC. This regimen can be an additional treatment option for second-line chemotherapy in WT KRAS mCRC. Clinical trial information: UMIN000004659.

Independent validation of effect of HSD3B1 genotype on response to androgen deprivation therapy (ADT) in hormone-sensitive prostate cancer (HSPC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 172-172
Author(s):  
Andrew W. Hahn ◽  
David Michael Gill ◽  
Austin Poole ◽  
James M. Farnham ◽  
Lisa A Cannon-Albright ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Salt Lake ◽  
Progression Free Survival ◽  
Castration Resistance ◽  
Wild Type ◽  
Adrenal Androgen ◽  
Type Group ◽  
Significant Difference ◽  
Variant Alleles ◽  
Independent Cohort

172 Background: A germline inherited polymorphic variant (1245A→C) in the HSD3B1 gene was recently reported to correlate with shorter duration of response to ADT in men with HSPC (Hearn JW, Lancet Oncology, 2016). HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Presence of one or more variant alleles was associated with shorter response to ADT compared to those with no variant alleles of this gene. Objective of this study was to validate these results in an independent cohort. Methods: Clinical data and samples were from a prospectively maintained prostate cancer registry at the University of Utah (Salt Lake City, UT). Genotyping was performed as described by Hearn at al. Primary endpoint was progression-free survival on ADT, i.e time to onset of castration resistance. We performed pre-specified multivariate analyses to assess the independent predictive value of HSD3B1 genotype on PFS on ADT (Table). Results: 102 men with new mHSPC met eligibility and included in the analysis. The allelic frequency of the HSD3B1 (1245C) variant in our cohort was 31%, i.e. similar to that reported by Hearn et al. In multivariate analysis, those men in the homozygous variant group had significantly shorter PFS in comparison to those in the homozygous wild type group; no significant difference in PFS was observed in those men in the heterozygous group compared to those in the homozygous wild type group (Table). Conclusions: HSD3B1(1245C) predicted inferior response to ADT in our independent cohort of men with mHSPC. We also confirm that this polymorphism is quite common in this population. [Table: see text]

Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)

2012 ◽  
Vol 30 (14) ◽  
pp. 1620-1627 ◽  
Author(s):  
Alice Dewdney ◽  
David Cunningham ◽  
Josep Tabernero ◽  
Jaume Capdevila ◽  
Bengt Glimelius ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Complete Response ◽  
Wild Type ◽  
End Point ◽  
Randomized Phase Ii ◽  
Biomarker Analysis ◽  
In The Wild

Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. Patients and Methods Patients with operable magnetic resonance imaging–defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. Results One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. Conclusion Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

scholarly journals Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma

Blood ◽  
2019 ◽  
Vol 133 (18) ◽  
pp. 1953-1963 ◽  
Author(s):  
Thierry Facon ◽  
Jae Hoon Lee ◽  
Philippe Moreau ◽  
Ruben Niesvizky ◽  
Meletios Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Intention To Treat ◽  
Significant Difference ◽  
Grade 3

Abstract The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4. The primary endpoint was progression-free survival (PFS). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n = 478; VMP, n = 477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; P = .159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease–negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 peripheral neuropathy was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. This trial was registered at www.clinicaltrials.gov as #NCT01818752.

Treatment of advanced mucosal melanoma in the immunotherapy era: A joint institutional case series.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21503-e21503
Author(s):  
Abigail Gee ◽  
Hannah Taylor ◽  
Christopher Herbert ◽  
Tania Tillett ◽  
Helen Winter
Keyword(s):  
Case Series ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Poor Response ◽  
Complete Response ◽  
Mucosal Melanoma ◽  
Treatment Modalities ◽  
Second Line ◽  
Wild Type ◽  
Treatment Pathways

e21503 Background: Treatment pathways for malignant melanoma have changed dramatically in recent years, with the advent of immunotherapy. Mucosal melanoma is a rare subtype, representing 1-2% of melanomas in Caucasians, with higher incidence reported in other populations. They commonly present at an advanced stage due to their occult, UV naïve location. Rarity limits adequate trial exposure and the literature offers contradictory data on the benefits of immune checkpoint inhibitor (ICI) therapy in this group. Methods: Patient databases at two specialised treatment centres were searched to identify all patients with mucosal melanoma treated with ICI therapy between 01.10.15 and 30.09.19. All patients were reviewed at the regional multi-disciplinary team meeting. Patient demographics, pathology reports, mutation status, stage at start of treatment and prior treatment modalities were noted. Results: Ten patients were identified with a median age 73 years (range 32-80) and M:F ratio of 4:6. The site of the primary cancer was head and neck in 5 cases, gastrointestinal in 3 cases and genitourinary in 2 cases. All patients were BRAF wild type. C-Kit was wild type in 3 patients tested. The median number of cycles of first line ICI was 5.5 (range 1 – 45). At first radiological assessment 7 patients had progressive disease (PD), 2 patients had stable disease and one patient had a complete response (CR). Two patients progressed to second line therapy with a second ICI. One of these demonstrated a partial response after a further 9 months of treatment and had a progression-free survival (PFS) of 30.1 months on second line treatment. One patient received 3 cycles of dual ICI therapy (ipilimumab/nivolumab) but demonstrated PD after 1.5 months. The longest surviving patient currently has a PFS of 43 months. He achieved a CR after just 3 months of pembrolizumab and completed a total of 18 cycles before switching to surveillance. Conclusions: The joint institutional case series demonstrates a poor response to ICI therapy in the majority of patients, yet as commonly reported, response when it occurs can be remarkable. Recent studies have shown increased overall response rate when anti-vascular endothelial growth factor therapies are added to cytotoxics or ICI. Further investigation of this rare subtype is required to identify predictive biomarkers of response to ICI therapy and other targeted and combination treatments.

scholarly journals Cetuximab versus bevacizumab following prior FOLFOXIRI and bevacizumab in postmenopausal women with advanced KRAS and BRAF wild-type colorectal cancer: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunlong Huang ◽  
Xiaoyuan Gu ◽  
Xianshang Zeng ◽  
Baomin Chen ◽  
Weiguang Yu ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Primary Endpoints ◽  
Significant Difference ◽  
Inductive Treatment ◽  
Advanced Colorectal Carcinoma

Abstract Background An upgraded understanding of factors (sex/estrogen) associated with survival benefit in advanced colorectal carcinoma (CRC) could improve personalised management and provide innovative insights into anti-tumour mechanisms. The aim of this study was to assess the efficacy and safety of cetuximab (CET) versus bevacizumab (BEV) following prior 12 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus BEV in postmenopausal women with advanced KRAS and BRAF wild-type (wt) CRC. Methods Prospectively maintained databases were reviewed from 2013 to 2017 to assess postmenopausal women with advanced KRAS and BRAF wt CRC who received up to 12 cycles of FOLFOXIRI plus BEV inductive treatment, followed by CET or BEV maintenance treatment. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rate. The secondary endpoint was the rate of adverse events (AEs). Results At a median follow-up of 27.0 months (IQR 25.1–29.2), significant difference was detected in median OS (17.7 months [95% confidence interval [CI], 16.2–18.6] for CET vs. 11.7 months [95% CI, 10.4–12.8] for BEV; hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; p=0.007); Median PFS was 10.7 months (95% CI, 9.8–11.3) for CET vs. 8.4 months (95% CI, 7.2–9.6) for BEV (HR, 0.67; 95% CI 0.47–0.94; p=0.02). Dose reduction due to intolerable AEs occurred in 29 cases (24 [24.0%] for CET vs. 5 [4.8%] for BEV; p< 0.001). Conclusions CET tends to be superior survival benefit when compared with BEV, with tolerated AEs.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

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