EP-1463: Phase II study of adaptive high-dose neoadjuvant radiotherapy in high risk rectal cancer

Abstract Background Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer. Methods We performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stage II and stage III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS). Results Between August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29–77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of ‘0’ and 14 had scores of ‘1’. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8–78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7). Conclusions Postoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides adequate 3-year DFS prospects. Trial registration This clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.

Download Full-text

A phase II study of neoadjuvant FOLFOXIRI followed by concurrent capecitabine and radiotherapy for high risk rectal cancer

Annals of Oncology ◽

10.1093/annonc/mdx261.363 ◽

2017 ◽

Vol 28 ◽

pp. iii129-iii130

Author(s):

Brigette Ma ◽

Janet Lee ◽

Michael Cheung ◽

Simon Chu ◽

Dennis Ng ◽

...

Keyword(s):

Rectal Cancer ◽

High Risk ◽

Phase Ii ◽

Phase Ii Study

Download Full-text

Phase II study of neoadjuvant high-dose ifosfamide with concurrent radiotherapy followed by surgical resection in high-risk soft tissue sarcoma: A Spanish Group for Research on Sarcomas (GEIS) study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10052 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10052-10052 ◽

Cited By ~ 3

Author(s):

Xavier Garcia del Muro ◽

Antonio Lopez-Pousa ◽

Maria Jose Flor ◽

Andrés Redondo ◽

Josefina Cruz Jurado ◽

...

Keyword(s):

High Risk ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Surgical Resection ◽

Phase Ii ◽

Phase Ii Study ◽

Pathologic Response ◽

Radiation Dermatitis ◽

Study Endpoint ◽

High Dose

10052 Background: High-dose ifosfamide (HDI) has shown promising activity as single agent in first-line chemotherapy for advanced soft tissue sarcoma (STS). The purpose of this study was to assess the activity and toxicity of a preoperative doxorubicin-free regimen of HDI given concurrently with radiotherapy (RT) and followed by surgery in patients (pts) with localized high-risk STS. Methods: Pts with localized > 5 cm grade 2-3 and deep STS of the extremities and trunk wall, ≤65 years, no prior chemotherapy and ECOG PS 0-1 were enrolled in this multicenter phase II study. Pts received 3 cycles of preoperative HDI at a dose of 12 gr/m2 by continuous infusion over 5 days every 3 weeks, with mesna and prophylactic GCSF support, and concomitant external beam RT to a total dose of 50 Gy, followed by surgical resection. Postoperatively, pts with pathological response received 2 cycles of HDI and those with positive surgical margins 16 Gy of RT. The primary study endpoint was pathologic response (≥ 95% pathologic necrosis). A Simon 2-stage design (response rate P0=15%, P1=35%, α=0.10, β=0.10) required at least 2 responses in the first 17 pts to expand to a second cohort, and 7/32 responses to be considered of positive. Results: From March 08 to December 10, 34 pts were included. Two pts were ineligible. Median age was 54 (18-65). Tumor location was extremity (28 pts) and trunk wall (4). Preoperative planned treatment was completed in 87.5% pts. HDI was completed in 87.5% pts while RT in 94% pts. Grade 3-4 toxicities included neutropenic fever (3 pts), anemia (4), asthenia (2), infection (2) and radiation dermatitis (2). 31 pts underwent surgery: 27 were R0 resections, of which 2 were amputations, and 4 were R1 resections. Pathologic response was ≥ 95% necrosis in 9 pts (28%) and 50%-94% necrosis in 12 pts. After a median follow-up of 21 months, estimated 2-year rates for disease-free survival and overall survival were 58% (95%CI, 40%-77%) and 77% (95%CI, 61%-93%), respectively. Conclusions: Preoperative treatment with HDI given concurrently with RT in pts with high-risk STS is feasible and safe, yielding promising pathologic response rates.

Download Full-text

Phase II study of vorinostat (V) in combination with idarubicin and high-dose cytarabine (IA) as front-line therapy in patients (pts) with high-risk myelodyplsatic syndrome (MDS) or acute myeloid leukemia (AML)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7004 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7004-7004

Author(s):

E. Jabbour ◽

S. Faderl ◽

F. Ravandi ◽

M. Konopleva ◽

S. Verstovsek ◽

...

Keyword(s):

High Risk ◽

Phase Ii ◽

Phase Ii Study ◽

Ex Vivo ◽

Phase 1 ◽

High Dose ◽

Front Line ◽

Line Therapy ◽

Grade 3

7004 Background: Standard induction therapy for pts with AML has not changed over the last 2 decades nor has the outcome of these pts. We demonstrated in vitro and ex vivo that the combination of an histone deacetylase inhibitor with anthraycline is synergistic (Blood 2006;108:1174); an effect that could be mediated by activation of DNA damage/repair pathways, and found that such combination is safe in phase 1 trial (Blood 2007;110:1842). We designed a phase II study of V with IA as front-line therapy for MDS/AML. Methods: Pts with untreated int-2/high-risk MDS or AML ages 15–65 with adequate liver and renal functions and PS, and EF ≥ 50% were eligible. Pts with CBF were excluded. Initial dose of V was 500 mg orally TID for 3 days followed on day 4 by IA (I:12 mg/m2/dx3; A:1.5g/m2/dx4 over 24 hrs). After induction and if in CR, pt can receive 5 cycles of consolidation with V at the same dose and IA (I:8 mg/m2/dx2; A:0.75g/m2/dx3 over 24 hours) followed by 1 year of maintenance with V. The study was powered to demonstrate improvement in PFS at 7 months and acceptable toxicity. Prior to formal initiation of the phase II, the study had a “run-in” phase to confirm the safety of the triple combination. Correlative studies include analysis of DNA repair/damage pathways. Results: 22 pts have been registered. 3 pts with relapsed/refractory AML were treated in the run-in phase. No excess toxicity was observed; 2 achieved CR and 1 CRp. Following these, 19 pts were enrolled on the phase 2 portion. 17 pts were evaluable. Median age was 49 years. Median WBC at presentation was 12.75 x 109/L. Cytogenetic analysis were abnormal in 12 (71%), complex in 10 (59%). 8 (47%) had secondary disease. 4 (23%) were Flt-3 positive. No unexpected grade 3/4 toxicities have been observed. The CR rate was 82%. 1 pt acheived a marrow CR and 2 pts died during induction. CR were universally associated with CG response. All Flt-3+ pts achieved a CR. Only 2 pts (14%) have relapsed (4 and 5 months). The median PFS has not been reached. Conclusions: The combination of IA and V is safe and active in AML/MDS. No stopping rule has been met. Results will be compared with those of a parallel IA study at MDACC. Correlative analysis are ongoing. [Table: see text]

Download Full-text