scholarly journals Dose escalation in advanced floor of the mouth cancer: a pilot study using a combination of IMRT and stereotactic boost

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tomáš Blažek ◽  
Zuzana Zděblová Čermáková ◽  
Lukáš Knybel ◽  
Pavel Hurník ◽  
Jan Štembírek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Surgical Treatment ◽  
Dose Escalation ◽  
External Beam Radiotherapy ◽  
Progression Free Survival ◽  
Invasive Approach ◽  
Fractionated Radiotherapy ◽  
Accelerated Radiotherapy ◽  
Floor Of The Mouth ◽  
Local Progression

Abstract Purpose We evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer. Methods Thirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70–72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables—tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4. Results After a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%). Conclusion The combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.

Phase I/II dose-escalation study of VB-111, an antiangiogenic gene therapy, in patients with recurrent glioblastoma multiforme.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS2102-TPS2102 ◽  
Author(s):  
Andrew Jacob Brenner ◽  
Yael Cohen ◽  
James J Vredenburgh ◽  
Katherine B. Peters ◽  
Eyal Breitbart ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Phase I ◽  
Dose Escalation ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
High Dose ◽  
Recurrent Glioblastoma Multiforme ◽  
Dose Escalation Study ◽  
Recurrent Gbm

TPS2102 Background: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a fas-chimera transgene in angiogenic endothelial cells. In a phase I/II dose-escalation study, safety and efficacy of VB-111 in patients with recurrent Glioblastoma Multiforme (GBM) were evaluated. Methods: VB-111 was administered as a single intravenous infusion at escalating doses from 1x1012 to 3x1012 viral particles (VPs), followed by repeat doses of 3x1012 or 1x1013every 2 months. Assessments included safety, pharmacokinetics, tumor response (RANO criteria) and overall survival (OS). Results: Twenty eight patients aged 26 – 74 years at 3 medical centers in the US received up to 8 repeat doses of VB-111. The median OS was 360 [range: 70-574] and 266 days [range: 28-664] for patients receiving at least one dose of 1x1013VPs (high dose) vs. subjects who received lower doses, respectively (p NS). Progression free survival was 87 vs 55 days for patients who received high dose and for lower doses, respectively (p = 0.01). Median follow-up was 232 days. Three patients had a partial response (PR) at 82, 86 and 408 days post initial VB-111 dosing. Twenty one of the patients who progressed on VB-111 treatment received bevacizumab off study; 7 of the 15 evaluable patients (47%) had a PR compared to 30% expected according to literature. VB-111 was safe and well tolerated, 53 adverse events were reported, 14 were classified as possibly related to VB-111. All events were of CTCAE grade 1-2 except one grade 3 pulmonary embolism. There were no study related deaths. One patient developed peri-tumoral edema, which resolved with corticosteroid therapy. Events occurring in > 10% of the patients included headache and fatigue. Conclusions: VB-111 was safe and well tolerated in patients with recurrent GBM with repeat doses of up to 1x1013 VPs. Tumor responses were seen. Overall survival was about 3 months longer than historical data in recurrent GBM, including standard of care anti-angiogenic agents. Data suggests that VB-111 potentiates the response to bevacizumab given at further progression. Clinical trial information: NCT01260506.

Efficacy and dosimetry prognostic factors of image guided 125I seed implantation for locally recurrent soft tissue sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11073-11073
Author(s):  
Weijuan Jiang ◽  
Ping Jiang ◽  
Ang Qu ◽  
Junjie Wang ◽  
Haitao Sun
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Ct Guided ◽  
Free Survival ◽  
Seed Implantation ◽  
Local Progression

11073 Background: To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. Methods: The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Results: Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1~144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI ( > 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 ( > 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Conclusions: Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.

scholarly journals Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study

2016 ◽  
Vol 16 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Tiziana Comito ◽  
L. Cozzi ◽  
E. Clerici ◽  
C. Franzese ◽  
A. Tozzi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Stereotactic Body Radiotherapy ◽  
Therapeutic Option ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Local Progression

Purpose: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. Materials and Methods: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. Results: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate ( P < .03) and multivariate analyses ( P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size ( P < .001) and freedom from local progression ( P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression ( P < .035), tumor diameter ( P < .002), and computed tomography before stereotactic body radiotherapy ( P < .001) were significantly correlated with overall survival from diagnosis. Conclusion: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.

scholarly journals 12 × 6 Gy stereotactic radiotherapy for lung tumors. Is there a difference in response between lung metastases and primary bronchial carcinoma?

2021 ◽  
Author(s):  
Dorota Lubgan ◽  
Sabine Semrau ◽  
Ulrike Lambrecht ◽  
Udo S. Gaipl ◽  
Rainer Fietkau
Keyword(s):  
Overall Survival ◽  
Malignant Melanoma ◽  
Stereotactic Radiotherapy ◽  
Cox Regression ◽  
Pulmonary Metastases ◽  
Bronchial Carcinoma ◽  
Progression Free Survival ◽  
Female Gender ◽  
Free Survival ◽  
Local Progression

Abstract Purpose The aim of this study was to evaluate the safety and long-term tumor control after stereotactic radiotherapy (SRT) with 12 × 6 Gy of patients with primary bronchial carcinoma (BC) or with pulmonary metastases (MET) of various solid tumors. Local progression-free survival (LPFS), progression-free survival (PFS), overall survival (OS), and prognostic factors were compared. Methods Between May 2012 and January 2020, 168 patients with 206 pulmonary lesions (170 MET and 36 primary BC) were treated with 12 × 6 Gy (BED10 116 Gy). The irradiated pulmonary MET were from the following cancers: 47 (27.6%) head and neck, 37 (21.8%) rectum or colon, 30 (17.6%) bronchial, 13 (7.6%) malignant melanoma, 9 (5.3%) esophageal, 9 (5.3%) sarcoma, and 25 (14.8%) other. Results The median follow-up was 16.26 months (range: 0.46–89.34) for BC and 19.18 months (0.89–91.11) for MET. Survival rates at 3 years were: OS 43% for BC and 35% for MET; LPFS BC 96% and MET 85%; PFS BC 35% and MET 29%. The most frequently observed grade 3 adverse events (AEs) were pneumonitis (5.9% BC, 4.8% MET), pulmonary fibrosis (2.9% BC, 4% MET), and pulmonary embolism (2.9% BC, 0.8% MET). The favorable prognostic effects on overall survival of patients with MET were female gender (log-rank: p < 0.001), no systemic progression (log-rank; p = 0.048, multivariate COX regression p = 0.039), and malignant melanoma histology (log-rank; p = 0.015, multivariate COX regression p = 0.020). For patients with BC, it was tumor location within the lower lobe (vs. upper lobe, log-rank p = 0.027). LPFS of patients with metastatic disease was beneficially influenced by female gender (log-rank: p = 0.049). Conclusion The treatment concept of 12 × 6 Gy is associated with 96% local progression-free survival for BC and 85% for pulmonary metastases after 3 years. There was no difference in response after SRT of primary lung carcinoma or pulmonary metastases.

scholarly journals Colorectal cancer metastases to the lungs: outcomes of surgical treatment and prognostic factors

2020 ◽  
Vol 10 (2) ◽  
pp. 33-41
Author(s):  
B. B. Akhmedov ◽  
P. V. Kononets ◽  
M. Yu. Fedyanin ◽  
Z. Z. Mamedli ◽  
S. S. Gordeev ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Surgical Treatment ◽  
Survival Rate ◽  
Postoperative Complications ◽  
Progression Free Survival ◽  
Free Survival ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Objective: to evaluate short-term and long-term outcomes of surgical treatment for colorectal cancer metastases to the lungs and to analyze factors affecting the efficacy of surgery. Materials and methods. This study included 211 patients with colorectal cancer metastases to the lungs treated between 1994 and 2014. We enrolled patients with resectable or conventionally resectable metastases (according to chest computed tomography evaluated by a thoracic surgeon); the exclusion criteria were as follows: multiple primary tumors and age more than 85 years. We assessed the type of surgeries, frequency of R0 resections, incidence of postoperative complications, overall survival, and progression-free survival. Results. One hundred and sixty-two patients out of 211 (76.8 %) have undergone atypical lung resection. Forty-nine patients (23.2 %) have undergone pneumonectomy, bilobectomy, or lobectomy. The majority of patients (96.2 %) have had R0 resection, whereas 2.9 % of study participants have had R1 or R2 resections. One patient has undergone a trial surgery. Clinically significant postoperative complications were observed in 4 (2 %) patients; postoperative mortality was 0.5 % (1 case). The five-year overall survival rate was 52.7 %; the 5-year progression-free survival rate was 45.8 %. Development of metastases within 24 months after primary surgery was found to be a significant factor negatively affecting overall survival (hazard ratio 0.347; 95 % confidence interval 0.227–0.53; р <0.0001). Conclusions. Surgical treatment is currently the only truly effective treatment, which can improve long-term survival of patients with colorectal cancer metastases to the lungs; the best treatment results are achieved in patients with a relapse-free interval of more than 24 months. 

Recombinant adenoviral human p53 gene combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16011-e16011 ◽  
Author(s):  
Jihong Shu
Keyword(s):  
Overall Survival ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Progression Free Survival ◽  
P53 Gene ◽  
Intratumoral Injection ◽  
Comprehensive Treatment ◽  
Local Progression

e16011 Background: In head and neck cancer, p53 mutations are present in up 60% of head and neck cancers. Studies indicated p53 gene could increase both radio- and chemo-sensitivities. In this study, we investigate the effectiveness of recombinant adenoviral human p53 gene (rAd-p53) combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer. Methods: From May 2008 to Dec. 2011, 48 patients with an advanced unresectable head and neck cancer, 29 males and 18 females with an average of 61.3 years old, were included this study. Those patients were treated with intratumoral injection of rAd-p53 at a dose 1-3 ×1012 viral particles (VP) , once every 3 days for 6 times. Chemotherapy regimen consisted of cisplatin 60 mg/m2 on d1 and 5-Fu 600 mg/m2 on d1-5, given intravenously every 3 weeks for 3 cycles. Radiation were given at a dose of 2Gy/f, five fractions a week for a total dose 50~70Gy. Patients were monitored for response, long-term efficacy and adverse events. Results: The median follow-up time was 21.2 months (6~39 months). Overall response rate was 91.7% (44/48), 47.9% (23/48) of complete responses and 43.8% (23/48) of partial responses. One-year overall survival was 79.2% and local progression-free survival was 70.8%. At the last follow-up, the overall survival was 72.9%. Forty-six patients experienced self-limited fever after administration of p53. Conclusions: rAd-p53 gene therapy as a component of comprehensive treatment for advanced unresectable head and neck cancer showed significant beneficial effects.

Intra-operative radiation therapy as salvage treatment option for recurrent glioblastoma multiforme.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2535-2535
Author(s):  
Nidal Salim ◽  
Alexey Krivoshapkin ◽  
Daria Zvereva ◽  
Alexey Gaytan ◽  
Orkhan Abdullaev ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
External Beam Radiotherapy ◽  
Adjuvant Radiation ◽  
External Beam ◽  
Cerebral Tumor ◽  
Electronic Brachytherapy ◽  
Local Progression ◽  
Microsurgical Resection ◽  
Recurrent Gbm

2535 Background: Glioblastoma multiforme (GBM) is an extremely aggressive cerebral tumor with poor prognosis. The majority of patients relapse after the initial surgery plus adjuvant radiation and chemotherapy. In case of recurrence there is no established standard therapy. The optimal techniques for salvage re-irradiation are unclear, so that procedure poses a challenge. In contrast to traditional external beam radiotherapy (EBRT) intra-operative radiotherapy (IORT) may improve patient’s outcome at the cost of minimal side effects and short treatment duration. Methods: A total of 30 patients were treated with recurrent GBM between August 2016 and June 2019. All patients underwent maximal safe resection; patients were divided into IORT and EBRT groups. 15 patients were included in each group with similar clinical characteristics. All patients in IORT group underwent maximal safe microsurgical resection with subsequent intraoperative balloon electronic brachytherapy (IBEB) and no further adjuvant treatment. IBEB was performed using Axxent electronic brachytherapy device (Xoft Electronic Brachytherapy (eBx) System, USA. Patients in EBRT group underwent same surgery followed by external beam radiotherapy. Contrast-enhanced brain MRI with perfusion was performed within 24 hours of surgery +/- brain PET-CT with 18-FDOPA and then every 3 months. Both groups were also assigned to subgroups (≤ 2.5cm3 and > 2.5cm3) based on post-operative contrast-enhancing volume (POCEV). Median overall survival (OS) since diagnosis and local progression-free survival (locPFS) following the second surgery were analyzed. Possible toxicities and prognostic factors were also evaluated. Results: Median OS was 27 months in IORT group and 21 months in EBRT group. The locPFS range between 3.5 to 39 months in IORT group and only 2 to 10 months in group with EBRT. Kaplan-Meier OS curves in patients with POCEV ≤ 2.5cm3 showed more favorable outcomes for patients in the IORT group (p < 0.05). In patients with POCEV > 2.5cm3 the median OS was 17 months in IORT group and 13.5 months in EBRT group. Conclusions: IORT of recurrent GBM is feasible and provides encouraging local progression-free and overall survival; no high-grade radiation induced toxicities occur and further studies to establish this method are mandatory. The toxicity profile of additional IBEB was manageable. Maximal safe microsurgical resection is the most important prognostic factor and could determine the effectiveness of post-surgical IBEB.

Stereotactic Radiosurgery for Metastases in Eloquent Central Brain Locations

2015 ◽  
Vol 42 (5) ◽  
pp. 333-337 ◽  
Author(s):  
Fred Hsu ◽  
Alan Nichol ◽  
Roy Ma ◽  
Para Kouhestani ◽  
Brian Toyota ◽  
...  
Keyword(s):  
Overall Survival ◽  
Basal Ganglia ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Brain Radiotherapy ◽  
Local Progression ◽  
Central Brain

AbstractBackground: To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. Methods: We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. Results: For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Conclusions: Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.

Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma

2011 ◽  
Vol 115 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Yoshihiro Muragaki ◽  
Takashi Maruyama ◽  
Hiroshi Iseki ◽  
Masahiko Tanaka ◽  
Chie Shinohara ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Vaccine ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Fractionated Radiotherapy ◽  
Newly Diagnosed Glioblastoma ◽  
Analysis Of Results ◽  
Formalin Fixed ◽  
Fixed Tumor

Object The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme. Methods Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done—one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment. Results The median duration of overall survival was 19.8 months (95% CI 13.8–31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3–13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection. Conclusions The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.

Regorafenib dose escalation therapy for patients with refractory metastatic colorectal cancer (RECC Study).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 116-116
Author(s):  
Masato Nakamura ◽  
Takeshi Yamada ◽  
Shun Ishiyama ◽  
Masanobu Enomoto ◽  
Hajime Yokomizo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Dose Escalation ◽  
Kinase Inhibitor ◽  
Asian Population ◽  
Progression Free Survival ◽  
Weekly Dose ◽  
Correct Trial ◽  
Daily Dose

116 Background: Regorafenib, a multi-kinase inhibitor, significantly improved overall survival in previously treated metastatic colorectal cancer (mCRC) patients in the phase 3 CORRECT trial. Despite its significant benefits, various toxicities such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited regorafenib use. The toxicities occur soon after treatment initiation, typically within the first cycle, and later improve. Although the standard daily dose of regorafenib is 160 mg, physicians have adopted various dosing regimens in clinical practice, indicating the need to optimize the dosing strategy to maintain the antitumor benefits. The ReDOS study demonstrated the effectiveness of a weekly dose-escalating strategy (WDES) of regorafenib starting with a lower daily dose. We conducted the phase II RECC study to evaluate the safety and efficacy of WDES for regorafenib in an Asian population. Methods: Patients with sufficient organ function who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3 if no severe drug-related toxicities were observed. The primary endpoint was progression-free survival (PFS) and secondary endpoints were time to treatment failure (TTF), response rate (RR), overall survival (OS), and safety. Tumor response and progression were assessed radiologically every 8 weeks. Results: From March 2017 to November 2018, 57 eligible patients were enrolled and all started regorafenib at 80 mg/day. Thirty-five patients (61%) were subsequently escalated to 120 mg/day and 16 (28%) to 160 mg/day. Forty patients (70.2%) finished Cycle 2 at 8 weeks. Only 8 patients (14%) discontinued treatment because of adverse events. The median PFS was 1.9 months, RR was 0%, and disease control rate was 32%. The most frequent adverse event ≥grade 3 was hypertension (17.5%), followed by HFSR (14%). No treatment-related deaths occurred. Conclusions: Regorafenib dose escalation was well tolerated with PFS similar to that reported in the CORRECT study, indicating that WDES may represent an option for regorafenib administration. Clinical trial information: UMIN000028933.

Sign in / Sign up

Export Citation Format

Share Document