Purpose
This randomized phase II study was conducted to investigate the efficacy of cryotherapy in preventing peripheral neuropathy and dermatological adverse events in breast cancer patients treated ...with weekly paclitaxel.
Methods
Patients treated with 12 weekly doses of paclitaxel for breast cancer were randomized (1:1) into a cryotherapy or control group. The primary endpoint was the percentage of patients with a marked decrease in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The secondary endpoints were Patient Neurotoxicity Questionnaire (PNQ), Common Terminology Criteria for Adverse Event (CTCAE) for peripheral neuropathy, and FACT-Taxane score.
Results
Forty-four patients were randomly assigned to the cryotherapy (
n
= 22) or control groups (
n
= 22). The percentage of patients with a marked decrease in FACT-NTX scores was significantly lower in the cryotherapy group than in the control group (41 vs. 73%,
p
= 0.03). The incidence of CTCAE grade ≥ 2 sensory (
p
= 0.001) and motor peripheral neuropathy (
p
= 0.01), and PNQ grade D or higher for sensory peripheral neuropathy (
p
= 0.02), and decrease in the FACT-Taxane score (
p
= 0.02) were also significantly lower in the cryotherapy group than in the control group. There were no serious side effects associated with cryotherapy.
Conclusion
Cryotherapy is an effective approach for prevention of peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.
Metaplastic breast cancer (MBC) is characterized by the histological presence of a mixture of epithelial and mesenchymal-like elements. However, MBC responds poorly to chemotherapy. Due to its ...rarity, there is no well-defined treatment for MBC. Herein, we report the case of a 56-year-old woman who underwent a mastectomy and was diagnosed with MBC with osseous differentiation classified as pT4N0M1. After the operation, she was treated with adriamycin and cisplatin, which are standard osteosarcoma treatments, resulting in a partial response. However, to determine the proper chemotherapy treatment, knowledge of the metaplastic elements of the tumor is required.
Trastuzumab emtansine (T-DM1), an anti–erb-b2 receptor tyrosine kinase 2 (HER2) antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a ...phase II trial of T-DM1 monotherapy in relapsed NSCLC with documented HER2 positivity (an immunohistochemistry IHC score of 3+, both an IHC score of 2+ and fluorescence in situ hybridization positivity, or exon 20 mutation). This study was terminated early because of limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: median age, 67 years; male sex, 47%; performance status of 0 to 1, 80%; HER2 status IHC 3+, 33%; HER status IHC 2+/fluorescence in situ hybridization–positive, 20%; and exon 20 mutation, 47%. The median number of delivered cycles was 3 (range 1–11). One patient achieved a partial response with an objective response rate of 6.7% (90% confidence interval: 0.2–32.0). With a median follow-up time of 9.2 months, the median progression-free survival time and median survival time were 2.0 and 10.9 months, respectively. Grade 3 or 4 adverse events included thrombocytopenia (40%) and hepatotoxicity (20%) without any treatment-related deaths. T-DM1 had a limited efficacy for HER2-positive NSCLC in our cohort. Applying the concept of precision medicine to tumors appears challenging; thus, additional molecular approaches are warranted.
Objective This study examined the pharmacokinetics, safety and anti-tumor activity of docetaxel at a dose of 100 mg/m2 in Japanese patients with advanced or recurrent breast cancer. Methods Japanese ...patients with advanced or recurrent breast cancer received docetaxel at a dose of 100 mg/m2 intravenously every three weeks. The pharmacokinetics were assessed during the first cycle. The patients were allowed to receive supportive care drugs based on the indications and dosages in Japan. Results Six eligible patients aged 39-65 years old and 27 treatment cycles were analyzed. All patients experienced one or more adverse events (AEs). The common AEs were neutropenia, thrombocytopenia, alopecia, rash, diarrhea, neuropathy (sensory), fatigue, nausea, fever, hypoalbuminemia, alanine transaminase (ALT) increased, constipation, and taste alteration. Grade 3 or 4 AEs included neutropenia, leukopenia, anemia, lymphopenia, decreased appetite, γ-glutamyl transpeptidase (GTP) increased, aspartate transaminase (AST) increased, ALT increased, hypertension and cellulitis which were all reversible. There were no cases of febrile neutropenia, serious AEs or deaths. The median number of cycles was six. Dose reductions were not observed and most cycles were administered at their intended doses. No complete response and three partial responses were observed in four assessable patients with evaluable lesions. The maximum concentration and area under the blood concentration-time curve were 3,417.5 ng/mL and 4.35 μg・hr/mL (mean), respectively. Conclusion Docetaxel at a dose of 100 mg/m2 was tolerable with acceptable safety profiles and effective for Japanese patients with advanced or recurrent breast cancer with appropriate supportive therapies, and pharmacokinetic (PK) profiles which corresponded approximately with the findings of previous clinical studies.
The prognostic value of sentinel lymph node (SLN) metastases may be minimized by the limited disease burden of lymph node metastases and tailoring adjuvant therapy based on breast cancer biology. The ...aim of this study is to assess the prognostic significance of SLN metastasis in patients with cT1-2N0M0 breast cancer.
Between January 2006 and December 2015, 582 patients underwent SLN biopsy for cT1-2N0M0 breast cancers. cN0 was essentially diagnosed by ultrasound sonography. The prognostic values of SLN metastases were retrospectively evaluated.
Among 582 patients with cT1-2N0M0 breast cancer, 111 patients (19.1%) were positive for SLN metastasis, including 39 cases (6.7%) of micrometastasis and 72 cases (12.4%) of macrometastases. The median size of SLN metastasis was 3.0 mm (range 0.2-16 mm, mean 4.1 mm). In log-rank test, presence of SLN metastasis was not associated with breast cancer recurrence (p = 0.21); 5-year and 10-year recurrence-free survival (RFS) were 93.0% and 96.5%, and 93.0% and 90.4% in the SLN-positive and SLN-negative groups, respectively. In the propensity score matching cohort (n = 178), there was no significant difference in RFS between the SLN-positive and SLN-negative groups (p = 0.90). In Cox regression analysis, a continuous value of Ki67 expression was a significant prognostic factor (HR 1.03; 95% CI 1.01-1.05, p = 0.017).
SLN metastasis has a minimal impact on RFS for patients with cT1-2N0M0 breast cancer in the modern medical era. A proliferation marker is a better factor for poor prognosis than the presence of SLN metastases in this population.
This study evaluated the safety and feasibility of a technique of liver resection named dual-wield parenchymal transection technique (DWT), using cavitron ultrasonic surgical aspirator (CUSA) and ...water-jet scalpel simultaneously.
This multicenter, prospective, open-label, and single-arm phase I trial included patients aged 20 years or older with hepatic tumors indicated for surgical resection and scheduled for open radical resection. This study was conducted at two institutions affiliated with the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). The primary endpoint was the proportion of massive intraoperative blood loss (≥ 1000 mL). The secondary endpoints were the amount of blood loss, operative time, parenchymal transection speed, postoperative complications, and mortality. The safety endpoints were device failure and adverse events associated with devices.
From June 2022 to May 2023, 20 patients were enrolled; one was excluded and 19 were included in the full analysis set (FAS). In the FAS, segmentectomy was performed in nine cases, sectionectomy in four cases, and hemihepatectomy in six cases. Radical resection was achieved in all patients. Intraoperative blood loss greater than 1000 mL was observed in five patients (26.3%). The median amount of blood loss was 545 mL (range, 180-4413), and blood transfusions were performed on two patients (10.5%). The median operative time was 346 minutes (range, 238-543) and the median parenchymal transection speed was 1.2 cm
/minute (range, 0.5-5.1). Postoperative complications of Clavien-Dindo classification ≥ Grade 3 occurred in four patients (21.1%). No mortalities occurred in this study. In the safety analysis, there were no device failures or adverse events associated with devices.
This study demonstrated the safety and feasibility of DWT for liver resection. The efficacy of the DWT will be evaluated in future clinical trials.
IntroductionHepatocellular carcinoma (HCC) remains a major clinical problem as more than half of these cases recur after radical resection. Natural killer (NK) cells are at the forefront of the ...innate immune system and attack microcarcinomas and circulating tumour cells. The objective of this study was to evaluate the feasibility and toxicity of peripheral blood CD34+ stem cell-derived NK cell infusion after radical hepatectomy for HCC.Methods and analysisThis is an open-label, single-arm, single-centre phase I study. Patients who have undergone initial hepatectomy for HCC with three or more risk factors for recurrence (≥10 ng/mL of Alpha fetoprotein (AFP), ≥360 mAU/mL of PIVKA-II, multiple tumours and ≥3 peripheral blood circulating tumour cells) will be enrolled and be treated with three peripheral blood CD34+ stem cell-derived NK cell infusions every 3 months. The primary endpoint will be safety assessment including the type and severity of adverse events, frequency of occurrence and duration of occurrence. The secondary endpoints will include survival, effect of immune response and clinical laboratory test results.Ethics and disseminationEthical approval of the trial was obtained from the Certified Committee for Regenerative Medicine Hiroshima University in Japan. The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal.Trial registration numberjRCTb060200020.
In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC), overall survival (OS) as an ...endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed.
We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design). Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs. 1.04), the former exhibited greater progression-free survival-hazard ratios (PFS-HR) (mean, 0.40 vs. 1.01; P<0.01). A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%). The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01). An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%.
The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial.
The treatment outcome has been unsatisfactory for patients with non–small-cell lung cancer (NSCLC) refractory to standard first-line chemotherapy. Trastuzumab emtansine (T-DM1), an anti-HER2 antibody ...conjugated with a vinca alkaloid, has been approved for clinical use in HER2+ breast cancer in many countries. Approximately 5% of NSCLC tumors possess HER2 alterations, and T-DM1 has shown excellent antitumor effects against HER2+ lung cancer cell lines in preclinical models. Therefore, we hypothesized that T-DM1 could significantly inhibit the growth of HER2+ lung cancers. We have launched a nonrandomized phase II trial of T-DM1 monotherapy for patients with HER2+ lung cancers. The major eligibility criteria are as follows: age ≥ 20 years, pathologically diagnosed NSCLC with documented HER2 positivity (immunohistochemistry 3+, both immunohistochemistry 2+ and fluorescence in situ hybridization positive, or exon 20 insertion mutation), and previous chemotherapy. Thirty patients will receive T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint is the overall response rate. This trial will provide information on whether T-DM1 monotherapy is effective against HER2+ lung cancer.
Second warm ischemic injury during vascular anastomosis not only adversely affects immediate posttransplant function but also affects long-term patient and graft survival. We developed a pouch-type ...thermal barrier bag (TBB) composed of a transparent, biocompatible insulation material suitably designed for kidneys and conducted the first-in-human clinical trial.
A living-donor nephrectomy was performed using a minimum skin incision procedure. After back table preparation, the kidney graft was placed inside the TBB and preserved during vascular anastomosis. The graft surface temperature was measured before and after vascular anastomosis using a noncontact infrared thermometer. After completion of the anastomosis, the TBB was removed from the transplanted kidney before graft reperfusion. Clinical data, including patient characteristics and perioperative variables, were collected. The primary endpoint was safety, which was assessed by evaluating adverse events. The secondary endpoints were the feasibility, tolerability, and efficacy of the TBB in kidney transplant recipients.
Ten living-donor kidney transplant recipients with a median age of 56 y (range, 39-69 y) were enrolled in this study. No serious adverse events related to the TBB were observed. The median second warm ischemic time was 31 (27-39) min, and the median graft surface temperature at the end of anastomosis was 16.1 °C (12.8-18.7 °C).
TBB can maintain transplanted kidneys at a low temperature during vascular anastomosis, which contributes to the functional preservation of transplanted kidneys and stable transplant outcomes.
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