Weekly cetuximab (CET) plus oxaliplatin (OX), infusional 5-fluorouracil (5-FU) and radiation therapy (RT) as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC): A phase I study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

e15507 Background: CET, a chimeric monoclonal IgG1 antibody that targets the epidermal growth factor receptor (EGFR), has proven activity in a variety of SCC models in vitro and in vivo and has also been shown to enhance the activity of both chemo- and radiotherapy. Methods: Patients (pts) with locally advanced ESCC received CET for 2 weeks at an initial dose of 400mg/m2 (d - 15) i.v. followed by 250mg/m2(d -8) before they started a neoadjuvant dose escalation regimen. Pts received weekly CET 250mg/m2 plus RT 25 x 1.8 Gy (cumulative dose 45 Gy) d1–33. Cohort 1–3 received escalating doses of OX 45–50 mg/m2 d1,8,22,29 plus 5-FU 180–200–225 mg/m2/d; d1–5,8–12,15–19,22–26,29–33). Surgery was scheduled 4–6 weeks after RT. Toxicity was assessed according to NCI-CTC. Response was categorized according to the histopathologic score. Results: 15 pts were enrolled (2 female, 13 male; mean age 62 years, ECOG-PS 0 or 1). All pts had locally advanced SCC (uT2–4, cNx, cM0–1a) of the cervical (n=1), the upper (n=5) or the distal (n=7) esophagus. 6 pts were treated in cohort 1 and 3 pts in cohort 2 without any dose limiting toxicity (DLT). Of 6 pts treated in cohort 3, 1 pt developed grade 3 diarrhea and mucositis. All other observed toxicities were mild or moderate: anemia n=12, neutropenia n=2, thrombocytopenia n=3, nausea/vomiting n=8, mucositis n=6, diarrhea n=4, neuropathy n=4, hand-foot-syndrome n=8, skin rash n=14, no infection and no infusion-related reactions were observed. 12 pts underwent abdomino-thoracic esophagectomy with no postop. mortality; 3 pts were not resected. 8/12 resected pts had an R0 resection (67%) and 4 pts (33%) achieved a histopathological complete response (score 1a). Conclusions: 2 weeks of CET (400mg/m2 and 250mg/m2) followed by weekly CET (250mg/m2) plus OX 50mg/m2 d1,8,22,29, 5-FU 225 mg/m2/d d1–5,8–12,15–19,22–26,29–33 and RT 45 Gy (1.8Gy/f) was shown to be safe as neoadjuvant treatment for locally advanced ESCC. The anti-tumor activity of this regimen is promising and is being further investigated in an ongoing phase II study. [Table: see text]

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Neoadjuvant itraconazole (I) in patients (pts) with resectable basal cell carcinoma (BCC): A phase II multistage study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22081 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e22081-e22081

Author(s):

Rodrigo Perez Pereira ◽

Sergio Jobim Azevedo ◽

Juliano Cé Coelho ◽

Taiane Francieli Rebelatto ◽

Gabriela Lusa Viapiana ◽

...

Keyword(s):

Objective Response ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

R0 Resection ◽

Ki 67 ◽

Secondary Endpoints ◽

Grade 3 ◽

Ecog Ps ◽

Stage 1

e22081 Background: Targeting the hedgehog (HH) protein family pathway has consistently shown activity in locally advanced and metastatic BCC. Itraconazole is an affordable agent with known toxicity profile that demonstrates in vitro HH signaling inhibition, suggesting a possible role in BCC treatment. Initial results of a phase 2 study designed to investigate efficacy of Itraconazole as neoadjuvant treatment in patients with resectable BCC are reported. Methods: Eligible pts had biopsy-proven resectable BCC, ECOG PS 0-3, adequate organ function and measurable disease. Dosing of I consisted of 200mg twice daily for 60 days followed by surgery. Simon two-stage design was used to test a null rate of 5% vs. 20% (power = 0.80; α = 0.05, unilateral). If ≥1 of 13 pts in stage 1 have objective response (OR) according to RECIST 1.1 criteria, 14 more pts will be enrolled. If ≥4 of 27 pts have OR, the treatment is worthy of further study. Secondary endpoints include safety and change in Ki-67 and Gli1. Results: Thirteen pts with 14 measurable lesions enrolled from Jan/2018 to Feb/2019; 1 pt was not evaluable, but was included in safety analysis. Demographics and outcomes are summarized in Table. After 60 days of treatment, all patients had R0 resection as primary planned and 1 (8.3%) PR was observed. There were no progressions during the study. OR rate was 8.3%. No grade 3 AE or SAE were reported. 6 pts had grade 1 or 2 AEs at least possibly related to I including depression, headache, GPT elevation, diarrhea, abdominal pain and bilirubin elevation. Conclusions: Itraconazole showed initial anti-tumor activity in pts with resectable BCC, no safety concerns were observed. Study will proceed to Simon’s second stage. Clinical Trial Information: NCT03972748 , 47011715.0.0000.5327 . [Table: see text]

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740 CAMRELIZUMAB IN COMBINATION WITH PREOPERATIVE CHEMOTHERAPY FOR LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A SINGLE-ARM, OPEN-LABEL, PHASE II STUDY

Diseases of the Esophagus ◽

10.1093/dote/doab052.740 ◽

2021 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Feng Wang ◽

Yu Qi ◽

Xiangrui Meng ◽

Qingxia Fan

Keyword(s):

Phase Ii ◽

Preoperative Chemotherapy ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Reduction Rate ◽

Complete Response ◽

Pathologic Response ◽

R0 Resection ◽

Efficacy And Safety

Abstract At present, ESCC has a dismal prognosis with huge unmet clinical needs. With the potential benefit of combining PD-1 inhibitor with nCT, we conducted a phase II trial to assess the efficacy and safety of Camrelizumab plus nCT for locally advanced ESCC. Methods 45 patients (pts) with histologically confirmed stage II/III/IVa(cT2-4aN0-3 M0) ESCC were enrolled from February 2020 to March 2021.The study was divided into two stages, stage1: we administered 1 cycle of Camrelizumab for induction therapy (200 mg q2 weeks); stage2: pts received 2 cycle of Camrelizumab (200 mg every 3 weeks) plus docetaxel and nedaplatin, followed by surgery within 4 ~ 6 weeks after neoadjuvant therapy completion. Primary endpoint was major pathologic response (MPR). Secondary endpoints included pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS) and overall survival (OS). Results At the cutoff date of Mar 9, 2021, 45 eligible pts were enrolled, neoadjuvant treatment was completed in 39 pts. Thus far 32 pts were resected, all patients underwent an R0 resection. Postoperative pathology showed that TNM stage decreased in 28 pts with 87.5% reduction rate. 19 pts (59.38%) reached major pathologic response, 9 pts (28.13%) reached pathologic complete response (no surgery related mortality). A total of 75.56% had AEs with 13.33% of grade ≥ 3 AEs. Date for median DFS and OS were not matured. Conclusion Camrelizumab in combination with preoperative chemotherapy followed by surgery for locally advanced ESCC showed promising downstaging effect and MPR with good tolerance, and its efficacy and safety could be further studied in later trials. Clinical trial information: NCT03917966.

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Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4050 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4050-4050

Author(s):

Hongli Li ◽

Jingyu Deng ◽

Shaohua Ge ◽

Fenglin Zang ◽

Le Zhang ◽

...

Keyword(s):

Adverse Events ◽

Phase Ii ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Death Receptor ◽

Disease Free Survival ◽

Complete Response ◽

R0 Resection ◽

Combination Regimen

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

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Camrelizumab combined with FOLFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4536 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4536-4536

Author(s):

Ying Liu ◽

Guangsen Han ◽

Hongle Li ◽

Yuzhou Zhao ◽

Jing Zhuang ◽

...

Keyword(s):

Neoadjuvant Therapy ◽

Clinical Stage ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Complete Response ◽

R0 Resection ◽

Radical Gastrectomy ◽

Imaging Evaluation ◽

Gastroesophageal Junction Adenocarcinoma ◽

Ecog Ps

4536 Background: Neoadjuvant chemotherapy has been demonstrated to improve the pathological complete response(pCR) and 5-year survival rate of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). Immunotherapy has become a new promising treatment for advanced GC/GEJC. Therefore, we intended to evaluate the safety and efficacy of Camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC. Methods: Eligiblepatients were locally advanced GC/GEJC with clinical stage≥T2 and/or positive lymphoglandula confirmed by endoscopic ultrasonography (EUS) and imaging. They received 4 cycles neoadjuvant therapy which including Camrelizumab(200mg ivgtt D1), FOLFOX(Oxaliplatin 85mg/m2 ivgtt D1, 5-Fu 400mg/m2 iv D1, LV 200mg/m2 ivgtt D1, 5-Fu 2.4mg/m2 CIV 46 hours) every 14 days. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients without progression disease (PD) received D2 radical gastrectomy. The primary endpoint was pCR, the secondary endpoints were R0 resection rate and safety. Results: From July 24 2019 to January 31 2020, 16 patients were eligible. The median age was 57 years (29-72 years). A total of 11(69%) males and 5(31%) females, ECOG PS 0 (n=9, 56%), ECOG PS 1 (n=7, 44%). All the patients completed 4 cycles treatment and none of them was confirmed PD by image. One of the patients refused gastrectomy and withdraw from the study. The other 15 patients underwent operation. Unfortunately, intraperitoneal metastases were confirmed in 2 patients during operation. 13 patients received D2 radical gastrectomy and all of them experienced R0 resection. Among the 13 evaluable patients, 1 patient (8%) was observed pCR, 3 patients (23%) experienced TRG1, 10 patients (77%) achieved stage reduction. Notably, 8 patients (62%) had lymphonodus pCR. The grade 3-4 treatment-related AEs were neutropenia (n=3, 19%), leukopenia (n=2, 13%) and anorexia (n=1, 6%). No serious AEs resulted in termination of treatment. Either severe immune-related AEs or treatment-related death was not observed. Conclusions: Camrelizumab combined with FOLFOX as neoadjuvant regimen in patients with locally advanced GC/GEJC showed promising pCR with good tolerance. Clinical trial information: NCT03939962 . [Table: see text]

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Efficacy and safety of camrelizumab combined with FLOT versus FLOT alone as neoadjuvant therapy in patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16020 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16020-e16020

Author(s):

Ning Liu ◽

Zimin Liu ◽

Yanbing Zhou ◽

Zhaojian Niu ◽

Haitao Jiang ◽

...

Keyword(s):

Neoadjuvant Therapy ◽

Intraoperative Complications ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Tumour Regression ◽

R0 Resection ◽

Resection Rate ◽

Tumour Regression Grade ◽

Ecog Ps

e16020 Background: Docetaxel-based neoadjuvant chemotherapy has been suggested to be beneficial in patients with locally advanced gastric and gastro-oesophageal junction cancer (GC/GEJC). And immunotherapy also show promising treatment efficacy for advanced GC/GEJC. Here we compared the safety and efficacy of camrelizumab combined with chemotherapy versus chemotherapy alone as the neoadjuvant therapy for patients with resectable locally advanced GC/GEJC. Methods: Eligible patients diagnosed as resectable locally advanced GC/GEJC were randomized to receive neoadjuvant treatment, in arm A, the patients received FLOT alone (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2600 mg/m², every 2 weeks), in arm B, the patients received FLOT combined with camrelizumab(camrelizumab 200mg intravenously every 3 weeks). Eligible patients underwent gastrectomy with D2 lymph node dissection. The primary end point of this trial was pCR rate and R0 resection rate, and the secondary end points were ORR,PFS, OS and safety profile. Results: From January 15 2020 to January 15 2021, 24 patients were recruited (11 patients in arm A and 13 patients in arm B). 19 patients had completed planned neoadjuvant treatment for 4 cycles (9 pts in the arm A, 10 ptsin the arm B). Two patients in the arm A were waiting for gastrectomy. This analysis was based on the 17 pts. In the arm A, the median age was 61 years (47-72 years) and a total of 5 males and 4 females, ECOG PS 0 (n = 1), ECOG PS 1 (n = 8). In the arm B, the median age was 63 years (57-71 years) and a total of 9 males and 1 females, all patients with ECOG PS 1. The R0 resection rate was high in arm B compared with arm A (10/10,100% vs. 5/7, 71.4%). No pCR were observed in the two arms. Tumour regression grade were as follows:TRG1 [arm A 0% (0/7), arm B 10% (1/10)], TRG2 [arm A 43% (3/7), arm B 60% (6/10)], TRG3 [arm A 29% (2/7), arm B 30% (3/10)].There was a significantly higher proportion of patients achieved a postoperative ypN0 in the arm B than arm A(60% vs 0%), which had preoperative clinical stage cT3-4N+M0. Postoperative pathologic staging was as follows: ypT1 [arm A 14% (1/7); armB 30% (3/10)]. ypT2 [armA 0% (0/7); armB 30% (3/10)]. ypT3 [arm A 29% (2/7); arm B 20% (2/10)]. ypT4 [armA 29% (2/7); armB 20% (2/10)]. Neither serious intraoperative complications nor immune-related adverse events were observed during perioperation. Treatment-related AEs neutropenia and leukopenia were manageable and there was no treatment-related death. Conclusions: Camrelizumab combined with FLOT showed promising efficacy as neoadjuvant treatment for patients with locally advanced gastric or GEJ adenocarcinoma, with low complications and acceptable toxicity. Clinical trial information: ChiCTR2000030610.

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miRNA-148a Enhances the Treatment Response of Patients with Rectal Cancer to Chemoradiation and Promotes Apoptosis by Directly Targeting c-Met

Biomedicines ◽

10.3390/biomedicines9101371 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1371

Author(s):

Chun-Ming Huang ◽

Ming-Yii Huang ◽

Yen-Cheng Chen ◽

Po-Jung Chen ◽

Wei-Chih Su ◽

...

Keyword(s):

Rectal Cancer ◽

Cellular Proliferation ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Before And After

Patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) have an excellent prognosis, but only approximately 30% of patients achieve pCR. Therefore, identifying predictors of pCR is imperative. We employed a microRNA (miRNA) microarray to compare the miRNA profiles of patients with LARC who achieved pCR (pCR group, n = 5) with those who did not (non-pCR group, n = 5). The validation set confirmed that miRNA-148a was overexpressed in the pCR group (n = 11) compared with the non-pCR group (n = 40). Cell proliferation and clonogenic assays revealed that miRNA-148a overexpression radio-sensitized cancer cells and inhibited cellular proliferation, before and after irradiation (p < 0.01). Apoptosis assays demonstrated that miRNA-148a enhanced apoptosis before and after irradiation. Reporter assays revealed that c-Met was the direct target gene of miRNA-148a. An in vivo study indicated that miRNA-148a enhanced the irradiation-induced suppression of xenograft tumor growth (p < 0.01). miRNA-148a may be a biomarker of pCR following NACRT and can promote apoptosis and inhibit proliferation in CRC cells by directly targeting c-Met in vitro and enhancing tumor response to irradiation in vivo.

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Capecitabine and cisplatyl as neoadjuvant treatment of locally advanced nasopharyngeal carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e17036 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e17036-e17036

Author(s):

E. Kerboua

Keyword(s):

Nasopharyngeal Carcinoma ◽

Single Agent ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Stage Iv ◽

Complete Response ◽

Tolerability Profile ◽

Common Grade ◽

Hand Foot Syndrome ◽

Grade 3

e17036 Background: The main objective of this study is to evaluate the activity and safety of capecitabine (X) and cisplatyl (C) in patients (pts) with locally advanced nasopharyngeal carcinoma(NPC). Capecitabine was reported to have single-agent activity in advanced/metastatic NPC. Combination of X and C should provide a convenient and active regimen. Methods: Pts with undifferentiated NPC type were enrolled from July 2007 to September 2008. They received X 1,000 mg/m2orally bid on days 1–14 + C 75/m2 IV day 1 q 3W, Three cycles were administered in a neoadjuvant setting before radiotherapy. The primary endpoint was overall response rate (ORR). Results: Forty-one (41) pts have been enrolled 28 male/13 female with locally advanced NPC: 15 pts (36,6% ) were stage III (UICC 1997) 26 pts (63,3%) stage IV (n = 6 IVA and n = 20 IVB). All pts were evaluated for safety and 36 pts for response. ORR was 86% with 63,8% (n = 23) complete response (CR), 22,2% (n = 8) partial response (PR), 2 progression disease (PD) and 2 stable disease (SD). The most common grade 3/4 adverse events were diarrhea 4,8% (n = 2), neutropenia 7,3% (n = 3), thrombocytopenia 7,3% (n = 3), vomiting 9,7% (n = 4) . Two pts died from sepsis that was probably treatment-related. A hand-foot syndrome was observed in 25% of pts (grade 1/2). Conclusions: Preliminary results show that X plus C provide an active regimen with an acceptable tolerability profile as neoadjuvant chemotherapy for locally advanced NPC. This regimen requires a shorter hospital stay and is more convenient for pts compared with the gold standard 5-FU plus cisplatyl. No significant financial relationships to disclose.

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Capecitabine in Addition to Anthracycline- and Taxane-Based Neoadjuvant Treatment in Patients With Primary Breast Cancer: Phase III GeparQuattro Study

Journal of Clinical Oncology ◽

10.1200/jco.2009.23.8303 ◽

2010 ◽

Vol 28 (12) ◽

pp. 2015-2023 ◽

Cited By ~ 132

Author(s):

Gunter von Minckwitz ◽

Mahdi Rezai ◽

Sibylle Loibl ◽

Peter A. Fasching ◽

Jens Huober ◽

...

Keyword(s):

Locally Advanced ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Breast Conservation ◽

Growth Factor Receptor ◽

Complete Response ◽

Phase Iii ◽

The Difference ◽

Locally Advanced Tumors ◽

Clinically Node Positive

Purpose Capecitabine can be integrated either concomitantly or sequentially to anthracycline-plus-taxane–based regimens. Patients and Methods Patients with large operable or locally advanced tumors, with hormone receptor–negative tumors, or with receptor-positive tumors but also clinically node-positive disease were recruited to receive preoperatively four cycles of epirubicin plus cyclophosphamide (EC; epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2). Patients were then randomly assigned to four cycles of docetaxel (100 mg/m2), four cycles of docetaxel + capecitabine (TX; docetaxel 75 mg/m2 plus capecitabine 1,800 mg/m2), or four cycles of docetaxel (75 mg/m2) followed by four cycles of capecitabine (1,800 mg/m2; T-X). Patients with human epidermal growth factor receptor 2 (HER-2) –positive tumors received trastuzumab concomitantly with all cycles. Primary objectives were to assess the effect of docetaxel by comparing EC plus docetaxel versus EC plus TX and to assess the effect of duration by comparing EC plus TX versus EC plus T-X on pathologic complete response (pCR, without invasive/noninvasive breast tumor, regardless of nodal status) at surgery, irrespective of trastuzumab treatment. Results Of 1,509 patients starting EC, 1,421 were randomly assigned to docetaxel (n = 471), TX (n = 471), or T-X (n = 479). At surgery, pCR rates were 22.3%, 19.5%, and 22.3%, respectively; the difference for docetaxel (EC plus docetaxel v EC plus TX) was 2.8% (95% CI, −2.4% to 8.0%; P = .298).The difference for duration was −2.8% (95% CI, −8.0% to 2.4%; P = .298). Breast conservation rates were 70.1%, 68.4%, and 65.3%, respectively (P = .781 for docetaxel; P = .270 for duration). Concomitant but not sequential treatment with docetaxel was associated with more diarrhea; nail changes, and hand-foot-syndrome, but it was associated with less edema. Conclusion Adding capecitabine to or prolonging duration of neoadjuvant EC plus docetaxel does not result in higher efficacy at surgery.

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Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment

10.31234/osf.io/zhpa4 ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Triple Negative ◽

Growth Factor Receptor ◽

Engineered Nanoparticles ◽

Efficacy Evaluation ◽

Dual Action ◽

Epidermal Growth ◽

Laminin 411 ◽

Immunologic Analysis

Engineered nanoparticles are widely used for delivery of drugs but frequently lack proof of safetyfor cancer patient's treatment. All-in-one covalent nanodrugs of the third generation have beensynthesized based on a poly(β-L-malic acid) (PMLA) platform, targeting human triple-negativebreast cancer (TNBC). They significantly inhibited tumor growth in nude mice by blockingsynthesis of epidermal growth factor receptor, and α4 and β1 chains of laminin-411, the tumorvascular wall protein and angiogenesis marker. PMLA and nanodrug biocompatibility and toxicityat low and high dosages were evaluated in vitro and in vivo. The dual-action nanodrug and singleactionprecursor nanoconjugates were assessed under in vitro conditions and in vivo with multipletreatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in vivo withdifferent drugs included blood hematologic and immunologic analysis after multiple intravenousadministrations. The present study demonstrates that the dual-action nanoconju-gate is highlyeffective in preclinical TNBC treatment without side effects, supported by hematologic andimmunologic assays data. PMLA-based nanodrugs of the Polycefin™ family passed multipletoxicity and efficacy tests in vitro and in vivo on preclinical level and may prove to be optimizedand efficacious for the treatment of cancer patients in the future.

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The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-90220-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yu Zhang ◽

Zhaohui Zhong ◽

Mei Li ◽

Jingyi Chen ◽

Tingru Lin ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

The Cancer Genome Atlas ◽

Actin Dynamics ◽

Elevated Expression ◽

Sw480 Cells ◽

And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

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