ABSTRACT
INTRODUCTION: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration-resistant diagnosis. Optimal first-line therapy for those with different prognoses is unknown. METHODS: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan-Meier methods to examine prostate specific antigen (PSA) progression-free and overall survival (OS) according to prognostic group and first-line therapy, and multivariable cox regression to determine variables associated with survival outcomes. RESULTS: Among 4135 patients, median PSA progression-free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6-7.3), and median OS 18.8 months (95% CI 18.0-19.6), ranging from 5.7 months (95% CI 4.8-7.0) in the poor prognosis group to 31.3 months (95% CI 29.7-32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2-3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34-2.31; intermediate HR 1.78, 95% CI 1.41-2.25; poor HR 8.01, 95% CI 2.93-21.9). CONCLUSION: Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First-line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.
Subject(s)
Androstenes , Docetaxel , Ketoconazole , Phenylthiohydantoin , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/blood , Aged , Retrospective Studies , Ketoconazole/therapeutic use , Prognosis , Middle Aged , Phenylthiohydantoin/therapeutic use , Phenylthiohydantoin/analogs & derivatives , Docetaxel/therapeutic use , Docetaxel/administration & dosage , Androstenes/therapeutic use , Prostate-Specific Antigen/blood , Benzamides/therapeutic use , Nitriles/therapeutic use , Aged, 80 and over , Progression-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Kaplan-Meier EstimateABSTRACT
Purpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract. Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX's shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines. Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of -20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells. Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.
Subject(s)
Docetaxel , Nanoparticles , Animals , Docetaxel/pharmacokinetics , Docetaxel/chemistry , Docetaxel/pharmacology , Docetaxel/administration & dosage , Humans , Administration, Oral , Nanoparticles/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Mice , Cell Line, Tumor , Coptis chinensis , Particle Size , Male , Drug Liberation , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Cell Survival/drug effects , Biological Availability , Solubility , Rats, Sprague-Dawley , Mice, Inbred BALB CABSTRACT
INTRODUCTION: Radiation recall reaction (RRR) is a rare inflammatory reaction developing in a previously irradiated field after a triggering agent. In pediatric patients, it is poorly understood and deficiently studied. Gemcitabine-docetaxel (G/D) in childhood cancer is mainly used as a salvage regimen for sarcomas. We aim to describe RRR triggered by G/D in children. PATIENTS AND METHODS: Retrospective review of 21 patients receiving G/D along with radiotherapy at two hospitals from 2010 until 2022. RRR was considered as any toxicity occurring after G/D administration in a previously irradiated field. RRR features were described. Fisher's and Mann-Whitney tests were utilized to analyze the risk factors involved. RESULTS: Sixteen episodes of RRR developed in 16 (76.2%) patients. RRR mainly involved deep layers of the skin (58%) and occurred predominantly after two G/D cycles. The mean time between radiotherapy and chemotherapy was 28.5 days (0-1359 days), and the mean radiation volume 391 mL (157-1810 mL) for RRR. RRR treatment was mainly systemic steroids, with partial responses in six of 11 (58%) patients. Re-exposure to G/D was associated with a high rate of recurrence in nine of 15 (56.2%), prompting drug discontinuation. The major risk factors for RRR after G/D include, without statistical significance, a larger volume of the irradiated field and a shorter interval between chemotherapy and radiotherapy. CONCLUSIONS: The incidence of RRR after G/D in the pediatric population is higher than previously reported. Drug re-exposure is usually followed by recurrence. Higher irradiated volumes and a shorter time to the start of chemotherapy could be related with an increased risk of RRR.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Deoxycytidine , Docetaxel , Gemcitabine , Humans , Retrospective Studies , Male , Female , Child , Deoxycytidine/analogs & derivatives , Deoxycytidine/adverse effects , Docetaxel/adverse effects , Docetaxel/administration & dosage , Adolescent , Risk Factors , Child, Preschool , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms/drug therapy , Neoplasms/radiotherapy , Follow-Up Studies , Infant , Radiodermatitis/etiology , Radiodermatitis/pathology , PrognosisABSTRACT
BACKGROUND/AIM: The COVID-19 pandemic brought many challenges in healthcare systems globally. Pegylated granulocyte colony stimulating factor (PEG-GCSF) is recommended to reduce febrile neutropenia (FN), however there are a few reports that G-CSF might worsen COVID-19 disease, and its appropriate use during the COVID-19 pandemic remains uncertain. This retrospective study aimed to analyze the association between PEG-GCSF use and COVID-19 infection and severity. PATIENTS AND METHODS: Breast cancer patients who received chemotherapy at the Nagoya Tokushukai General Hospital between October 2020 and April 2023 were included. Patients with suspected COVID-19 symptoms during each chemotherapy cycle underwent COVID-19 antigen testing. To assess the potential impact of PEG-GCSF on COVID-19 severity, we collected data on patient background, chemotherapy regimens, PEG-GCSF use, COVID-19 antigen tests, and COVID-19 infection from their medical records. RESULTS: Thirty patients received chemotherapy. In total, 71 cycles were administered comprising adriamycin and cyclophosphamide (AC; 37 cycles), docetaxel (DTX; 26 cycles) and docetaxel and cyclophosphamide (TC; eight cycles). Among those patients, suspected COVID-19 symptoms were observed in only one of 62 cycles of the three regimens (1.6%) with PEG-GCSF compared to two of nine cycles (22.2%) without PEG-GCSF (p=0.0405). However, because none developed COVID-19 infection during chemotherapy, we could not assess COVID-19 severity and PEG-GCSF use. CONCLUSION: A potential role of PEG-GCSF in reducing suspected COVID-19 symptoms during chemotherapy, reducing the anxiety and need for hospital visits, thus improving patients' quality of life, is suggested. These insights could contribute to optimizing the care of breast cancer patients in situations like the current pandemic.
Subject(s)
Breast Neoplasms , COVID-19 , Granulocyte Colony-Stimulating Factor , SARS-CoV-2 , Humans , Breast Neoplasms/drug therapy , COVID-19/epidemiology , COVID-19/prevention & control , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Middle Aged , Adult , Aged , Retrospective Studies , Polyethylene Glycols/therapeutic use , Polyethylene Glycols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Docetaxel/therapeutic use , Docetaxel/administration & dosage , PandemicsABSTRACT
BACKGROUND/AIM: In patients with metastatic castration-sensitive prostate cancer (mCSPC), upfront treatment intensification with the addition of new hormonal agents and/or docetaxel to androgen deprivation therapy (ADT) is recommended. However, this modality is potentially excessive in a subset of these patients. This study aimed to identify patients who may be eligible to omit upfront treatment intensification. PATIENTS AND METHODS: Patients with mCSPC who underwent ADT were enrolled. The association between undetectable prostate-specific antigen (PSA) (<0.2 ng/ml) after ADT initiation and overall or castration-resistance-free survival was evaluated. RESULTS: Ninety-seven out of the 242 enrolled patients had low-risk and/or low-volume cancer and were further analyzed. Of these, 45 (46.4%) patients achieved undetectable PSA. The median follow-up period after ADT initiation was 70 months. The median overall survival among patients with undetectable PSA was quite long, reaching 226 months and significantly longer than that among patients with detectable PSA [71 months, hazard ratio (HR)=0.27, 95% confidence interval (CI)=0.15-0.49, p<0.001]. Time to development of castration-resistance was also long and significantly longer in the undetectable PSA group than that in the detectable PSA group (median: 124 vs. 17 months, HR=0.20, 95% CI=0.12-0.34, p<0.001). CONCLUSION: Patients with low-risk and/or low-volume mCSPC showed long-term survival when undetectable PSA was achieved during conventional ADT. In these patients, skipping upfront treatment intensification does not seem to negatively impact survival.
Subject(s)
Androgen Antagonists , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Aged , Prostate-Specific Antigen/blood , Middle Aged , Androgen Antagonists/therapeutic use , Androgen Antagonists/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/mortality , Treatment Outcome , Neoplasm Metastasis , Aged, 80 and over , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/mortality , Docetaxel/administration & dosage , Docetaxel/therapeutic useABSTRACT
Background: Chemotherapeutic drugs have some drawbacks in antineoplastic therapy, mainly containing seriously toxic side effects caused by injection and multi-drug resistance (MDR). Co-delivery with two or more drugs via nanomicelles is a promising strategy to solve these problems. Oral chemotherapy is increasingly preferred owing to its potential to enhance the life quality of patients. Methods and Results: The study intended to develop mixed micelles using D-α-Tocopherol poly(ethylene glycol) 1000 succinate (TPGS) and soluplus for the co-encapsulation of docetaxel (DTX) and curcumin (CUR), marked as (DTX+CUR)-loaded mixed micelles, treating drug-resistant breast cancer by oral administration. The (DTX+CUR)-loaded mixed micelles had a uniform particle size (~64 nm), high drug loading and encapsulation efficiency, in vitro sustained-release properties and good pH-dependent stability. In vitro cell study, the (DTX+CUR)-loaded mixed micelles displayed the highest cellular uptake, cytotoxicity, cell apoptosis-inducing rates and cell ROS-inducing levels on MCF-7/Adr cells. Notably, in vivo pharmacokinetic studies, (DTX+CUR)-loaded mixed micelles enhanced markedly the oral absorption of DTX compared to pure DTX, with a relative oral bioavailability of 574%. The (DTX+CUR)-loaded mixed micelles by oral administration had the same anticancer efficacy as taxotere by injection in resistant breast cancer bearing mice. Conclusion: (DTX+CUR)-loaded mixed micelles could provide a potential formulation for treating drug-resistant breast cancers by oral administration.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Curcumin , Docetaxel , Drug Resistance, Neoplasm , Micelles , Polyethylene Glycols , Curcumin/pharmacokinetics , Curcumin/chemistry , Curcumin/administration & dosage , Curcumin/pharmacology , Docetaxel/pharmacokinetics , Docetaxel/administration & dosage , Docetaxel/chemistry , Docetaxel/pharmacology , Humans , Female , Animals , Breast Neoplasms/drug therapy , Administration, Oral , Drug Resistance, Neoplasm/drug effects , MCF-7 Cells , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Vitamin E/chemistry , Vitamin E/administration & dosage , Vitamin E/pharmacokinetics , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Polyvinyls/chemistry , Polyvinyls/pharmacokinetics , Polyvinyls/administration & dosage , Mice , Mice, Inbred BALB C , Particle Size , Taxoids/pharmacokinetics , Taxoids/administration & dosage , Taxoids/chemistry , Taxoids/pharmacology , Drug Liberation , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Based on the JCOG1109 trial, it is suggested that the combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) could potentially become a standard neoadjuvant chemotherapy regimen, alongside the conventional 5-fluorouracil and cisplatin (CF) therapy, for esophageal cancer. However, there are few reports on the impact of body composition changes associated with neoadjuvant chemotherapy on prognosis. AIM: Our study aimed to explore the effect of different neoadjuvant chemotherapy regimens on body composition during treatment and the impacts of body composition changes on their prognosis. METHODS AND RESULTS: This is a retrospective study of 215 patients with advanced thoracic esophageal cancer who had surgery after neoadjuvant chemotherapy from 2013 to 2019. Computed tomography scans were performed before and after neoadjuvant chemotherapy to assess body composition. Skeletal muscle mass index (SMI) was calculated by dividing total skeletal muscle mass at the 3rd lumbar level by the square of height, while visceral and subcutaneous fat masses were measured at the level of umbilicus. Patients in the lowest 25% of both sexes were classified into the low visceral fat and low subcutaneous fat groups, respectively. Of the patients enrolled, 178 were male and 37 were female. Among them, 91 had clinical Stage II disease, and 124 had clinical Stage III disease. Additionally, 146 patients received neoadjuvant chemotherapy CF, and 69 received neoadjuvant chemotherapy DCF. Comparing the DCF and CF groups, the DCF group consisted of significantly younger patients (p < .01), a higher proportion of males (p = .03), and a greater number of clinical Stage III cases (p < .01). However, although percent change in SMI and visceral fat mass was not significantly different between two regimens, percent change in subcutaneous fat mass was significant in the DCF group. The major prognostic factors for patients undergoing surgery after neoadjuvant chemotherapy for thoracic esophageal cancer were clinical Stage III, transition to low visceral fat, and response rating (SD/PD), while the specific neoadjuvant chemotherapy regimen did not significantly influence the outcomes. CONCLUSION: This study suggests that prevention of the shift to low visceral fat throughout the neoadjuvant chemotherapy process should improve patient outcomes.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Body Composition , Cisplatin , Esophageal Neoplasms , Intra-Abdominal Fat , Neoadjuvant Therapy , Humans , Male , Female , Esophageal Neoplasms/pathology , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/therapy , Neoadjuvant Therapy/methods , Middle Aged , Retrospective Studies , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged , Cisplatin/administration & dosage , Docetaxel/administration & dosage , Fluorouracil/administration & dosage , Esophagectomy , Neoplasm Staging , AdultABSTRACT
The treatment of metastatic castration-sensitive prostate cancer (mCSPC) has seen remarkable breakthroughs over the last few years. Diagnostic and therapeutic advances have given rise to debates about risk stratification and optimal first-line treatment selection, as well as to concerns about potential overtreatment in a disease state with a highly heterogeneous clinical behavior. Here, we use case reports from our practice to review the clinical trials exploring intensified triplet regimens combining androgen deprivation therapy with second-generation androgen receptor signaling inhibitors and docetaxel, and we offer our recommendations on how to best select candidates for these novel combinations. Furthermore, the growing adoption of PET imaging with increasingly sensitive and prostate tissue-specific tracers replacing conventional staging technologies has led to the identification of a subset of low-volume mCSPC with nodal metastases which would otherwise not be considered abnormal by RECIST criteria. We describe our PSA-adapted approach to treatment in this unique population with non-measurable low-volume mCSPC which has not been specifically investigated in any phase III clinical trials. We also discuss ongoing clinical trials evaluating treatment de-escalation strategies. Finally, we review how local treatment modalities directed at the prostate or distant sites of disease in oligometastatic CSPC may benefit patients, and how we incorporate metastasis-directed therapy in the management of mCSPC.
Subject(s)
Neoplasm Metastasis , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Androgen Antagonists/therapeutic use , Docetaxel/therapeutic use , Docetaxel/administration & dosageABSTRACT
INTRODUCTION: Docetaxel plus ramucirumab (DTX + RAM) therapy is a standard treatment for previously treated lung cancer, but many adverse events have been reported. This retrospective study was conducted to examine if the side effects of DTX + RAM therapy can be minimized by the combined use of oral dexamethasone (DEX), and to assess the therapeutic effect of DTX + RAM in patients with recurrent lung cancer. METHODS: Forty patients with relapsed non-small cell lung cancer who underwent DTX + RAM therapy were divided into two groups based on the concomitant use of oral DEX, and the therapeutic effects and toxicities in the two groups were compared. RESULTS: The objective response rate (ORR) was significantly better in the DEX group (P = 0.0203). The median progression-free survival (PFS) was 5.20 months vs 2.87 months (P = 0.064) in the DEX and non-DEX groups, respectively. However, the median overall survival (OS) was significantly better in the DEX group (15.17 months vs 7.37 months, P = 0.0317). The frequency of fluid retention within six months of the start of treatment was 10.0% vs 42.5% in the DEX and non-DEX groups, respectively, with the fluid retention rate being significantly higher in the non-DEX group (P = 0.039).Conclusion: Concomitant use of oral DEX during DTX + RAM therapy may facilitate the long-term continuation of treatment and contribute to OS prolongation.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , Dexamethasone , Docetaxel , Lung Neoplasms , Ramucirumab , Humans , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Male , Female , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Retrospective Studies , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Middle Aged , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Adult , Administration, Oral , Neoplasm Recurrence, Local/drug therapy , Treatment OutcomeABSTRACT
INTRODUCTION: Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer. METHODS: In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail. RESULTS: When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth. CONCLUSION: The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.
Subject(s)
Diterpenes, Kaurane , Docetaxel , Esophageal Neoplasms , Liposomes , Diterpenes, Kaurane/pharmacology , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/administration & dosage , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Docetaxel/pharmacology , Docetaxel/administration & dosage , Docetaxel/chemistry , Liposomes/chemistry , Animals , Humans , Cell Line, Tumor , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Nanoparticles/chemistry , Particle Size , Xenograft Model Antitumor Assays , Drug Liberation , Drug Delivery Systems/methods , Mice, Nude , Mice, Inbred BALB C , Nanoparticle Drug Delivery System/chemistryABSTRACT
INTRODUCTION: Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. METHODS: Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. RESULTS: One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. CONCLUSION: In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Chemoradiotherapy, Adjuvant , Cisplatin , Docetaxel , Fluorouracil , Leucovorin , Neoplasm Staging , Stomach Neoplasms , Humans , Stomach Neoplasms/therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Male , Middle Aged , Female , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel/administration & dosage , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Aged , Adult , Retrospective Studies , Chemoradiotherapy, Adjuvant/methods , Leucovorin/administration & dosage , Leucovorin/therapeutic use , Treatment OutcomeABSTRACT
In perioperative chemotherapy for breast cancer, dexamethasone (DEX) is administered at high dose to prevent adverse effects. Abrupt cessation of high-dose DEX treatment induces fatigue, but the incidence of the fatigue is uncertain. In this study, we retrospectively evaluated the incidence of fatigue following DEX administration for supportive therapy and the improvement of fatigue with DEX tapering, a gradual reduction of the daily dose, in breast cancer patients. The subjects were 124 patients with breast cancer receiving epirubicin- or docetaxel-based regimens as perioperative chemotherapy. Of all patients, 16.1% of patients experienced fatigue after cessation of DEX administration. The severity of fatigue was grade 1 in 6.5% of patients, grade 2 in 8.1% of patients, and grade 3 in 1.6% of patients. There were no significant differences in dose and duration of DEX administration between the group with fatigue and the group without fatigue. In almost all patients with fatigue, DEX tapering was performed from the next cycle. The efficacy of DEX tapering was evaluated by comparing the grade and subjective symptoms. Following DEX tapering, the severity of fatigue was significantly reduced (p < 0.05), and the subjective symptom was improved in 94.7% of patients. Therefore, fatigue is occasionally induced after the cessation of DEX administration for supportive therapy in breast cancer patients. The tapering of DEX may be effective for fatigue.
Subject(s)
Breast Neoplasms , Dexamethasone , Fatigue , Humans , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Breast Neoplasms/surgery , Breast Neoplasms/drug therapy , Female , Retrospective Studies , Fatigue/drug therapy , Fatigue/etiology , Middle Aged , Adult , Aged , Incidence , Epirubicin/administration & dosage , Epirubicin/adverse effects , Epirubicin/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Perioperative Care/methods , Docetaxel/administration & dosage , Docetaxel/adverse effects , Docetaxel/therapeutic use , Drug Tapering , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic useABSTRACT
The administration of cabazitaxel for patients with castration-resistant prostate cancer (CRPC) requires prior docetaxel therapy. Sequential chemotherapy may have to be discontinued due to docetaxelassociated side effects. This study investigated the relationship between treatment outcome of docetaxel and cabazitaxel and their associated side effects. We retrospectively analyzed 69 patients with CRPC who had been administered docetaxel withand without subsequent cabazitaxel at Toyonaka Municipal Hospital from October 2014 to June 2022. Twenty-eight patients (41%) discontinued docetaxel because of side effects, and the median number of docetaxel cycles at discontinuation was 2 (range : 1-11). Fourteen of these patients received no treatment following docetaxel. A comparison of the 28 patients who had discontinued docetaxel due to side effects with 41 patients who had not revealed a significant difference in the total numbers of chemotherapy cycles (2.5 vs 9 ; Pï¼0.001) and time to treatment failure (56 days vs 301 days ; Pï¼ 0.001), with a trend toward shorter overall survival from the start of docetaxel treatment (259 days vs 512 days ; Pï¼0.06). Multivariate analysis identified discontinuation of docetaxel due to side effects (ORï¼0.07 ; Pï¼0.001) and lower hemoglobin (ORï¼0.01 ; Pï¼0.001) as significant factors inhibiting the introduction of cabazitaxel. Reducing the side effects of docetaxel, including early drug switching, may allow more CRPC patients to be reached with cabazitaxel. Consequently, the resulting taxane-based chemotherapy may contribute to an additional survival advantage.
Subject(s)
Docetaxel , Prostatic Neoplasms, Castration-Resistant , Taxoids , Humans , Male , Taxoids/adverse effects , Taxoids/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Docetaxel/administration & dosage , Docetaxel/adverse effects , Aged , Middle Aged , Retrospective Studies , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Treatment OutcomeABSTRACT
BACKGROUND: We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ). METHODS: This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue. RESULTS: Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P < .001) and grade 2/3 neuropathy (17% vs 7%; P = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations. CONCLUSION: FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation.CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944).
Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , Capecitabine , Docetaxel , Esophagogastric Junction , Fluorouracil , Leucovorin , Oxaliplatin , Receptor, ErbB-2 , Stomach Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Middle Aged , Female , Capecitabine/administration & dosage , Capecitabine/adverse effects , Docetaxel/administration & dosage , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Aged , Receptor, ErbB-2/genetics , Oxaliplatin/administration & dosage , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adult , Kaplan-Meier Estimate , Organoplatinum Compounds/administration & dosage , Microsatellite Instability , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathologyABSTRACT
The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxelâ +â cisplatinâ +â fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant ( P â <â 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group ( P â <â 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group ( P â <â 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Docetaxel , Fluorouracil , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Stomach Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Male , Female , Middle Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Fluorouracil/administration & dosage , Cisplatin/administration & dosage , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Interleukin-4 , Th1-Th2 Balance/drug effects , Aged , Th1 Cells/immunology , Th1 Cells/drug effects , Interferon-gamma , Th2 Cells/immunology , Th2 Cells/drug effects , AdultABSTRACT
PURPOSE: Common side effects of taxane chemotherapy are nail toxicity and peripheral neuropathy (CIPN) causing severe impact on the quality of life. Different methods of cryotherapy to prevent these side effects have been tested. We investigated the use of machine-controlled cooling of hands and feet to reduce nail toxicity and CIPN in patients receiving taxane chemotherapy. METHODS: Patients receiving Docetaxel (planned dose ≥ 300 mg/m2) or Paclitaxel (planned dose ≥ 720 mg/m2 - ) in the adjuvant or palliative setting of different cancers were included. The dominant hand and foot were cooled to approximately 10 °C using the Hilotherapy machine. The contralateral hand and foot were used as intrapatient comparison. The primary endpoint was the occurrence of any CIPN due to paclitaxel or nail toxicity due to Docetaxel. Both the intention to treat population (ITT) and the per protocol population (PPP) were analyzed. RESULTS: A total of 69 patients, 21 treated with Docetaxel and 48 with Paclitaxel, were included at our centre between 08/2020 and 08/2022. Nail toxicity due to Docetaxel was overall not significantly improved by cooling in the ITT or PPP but a significant benefit across visits was found for the ITT. CIPN due to Paclitaxel was numerically better in the ITT and significantly better in the PPP. A significant benefit of cooling on CIPN occurrence across visits was found for the ITT and the PPP. Cooling was very well tolerated. CONCLUSION: Cooling of hands and feet has a clinically meaningful impact on reducing occurrence of CIPN and nail toxicity on treatment with taxanes. Effects are more significant over time and are dose dependent. TRIAL REGISTRATION NUMBER: 2020-00381. Date of registration. 24th February 2020.
Subject(s)
Docetaxel , Nail Diseases , Paclitaxel , Peripheral Nervous System Diseases , Humans , Female , Prospective Studies , Middle Aged , Male , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & control , Aged , Docetaxel/administration & dosage , Docetaxel/adverse effects , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Nail Diseases/therapy , Nail Diseases/chemically induced , Neoplasms/drug therapy , Adult , Taxoids/adverse effects , Taxoids/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Cryotherapy/methods , Quality of LifeABSTRACT
PURPOSE: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. METHODS: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. RESULTS: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. CONCLUSION: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy.
Subject(s)
Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Cyclophosphamide , Docetaxel , Stomatitis , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Female , Docetaxel/administration & dosage , Docetaxel/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Middle Aged , Stomatitis/chemically induced , Stomatitis/epidemiology , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Anthracyclines/adverse effects , Anthracyclines/administration & dosage , Adult , Aged , Incidence , Taxoids/adverse effects , Taxoids/administration & dosage , Risk FactorsABSTRACT
High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate instrument. Correlative analyses included pharmacokinetics and oxidative stress markers. Eighty-nine percent of patients previously had three or more lines of therapy. The PSA50 response rate was 41% in the HDIVC group and 33% in the placebo group (P = 0.44), with comparable adverse event rates in both groups. There were no significant differences in Functional Assessment of Cancer Therapy-Prostate scores. The median radiographic progression-free survival was not significantly different between the HDIVC and placebo groups, with durations of 10.1 and 10.0 months (HR, 1.35; 95% confidence interval, 0.66-2.75; P = 0.40), respectively. The median overall survival was 15.2 months in the HDIVC group and 29.5 months in the placebo group (HR, 1.98; 95% confidence interval, 0.85-4.58; P = 0.11). HDIVC did not decrease F2-isoprostanes, indicators of oxidative stress. The study was suspended after prespecified interim analysis indicated futility in achieving primary endpoints. In this patient population, combining HDIVC with docetaxel did not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. Findings do not support the routine use of HDIVC in mCRPC treatment outside of clinical trials. SIGNIFICANCE: This is the first randomized, placebo-controlled, double-blind trial to evaluate HDIVC in cancer treatment. The addition of HDIVC to docetaxel in patients with mCRPC does not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. The routine use of HDIVC in mCRPC treatment is not supported outside of clinical trials.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Ascorbic Acid , Docetaxel , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/mortality , Ascorbic Acid/administration & dosage , Ascorbic Acid/therapeutic use , Ascorbic Acid/adverse effects , Aged , Double-Blind Method , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Administration, Intravenous , Quality of Life , Aged, 80 and over , Neoplasm MetastasisABSTRACT
BACKGROUND: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. RESULTS: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. CONCLUSIONS: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.
Subject(s)
Androgen Receptor Antagonists , Phenylthiohydantoin , Prostatic Neoplasms, Castration-Resistant , Proton Pump Inhibitors , Humans , Male , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Retrospective Studies , Androgen Receptor Antagonists/therapeutic use , Androgen Receptor Antagonists/pharmacology , Middle Aged , Phenylthiohydantoin/therapeutic use , Abiraterone Acetate/therapeutic use , Abiraterone Acetate/administration & dosage , Treatment Outcome , Aged, 80 and over , Benzamides , Nitriles/therapeutic use , Prostate-Specific Antigen/blood , Signal Transduction/drug effects , Receptors, Androgen/metabolism , Progression-Free Survival , Neoplasm Metastasis , Docetaxel/therapeutic use , Docetaxel/administration & dosageABSTRACT
Sinonasal squamous cell carcinoma (SNSCC) is the most common, high-aggressive sinonasal malignancies that have remained relatively stable poor outcomes over the past decade. As a first-line treatment for SNSCC, surgery plus adjuvant radiotherapy is recommended. However, complete surgical resection may not be appropriate due to the proximity of the nasal cavity and sinuses to key structures such as orbit or intracranial. Currently, immune checkpoint inhibitors (ICIs) have been established as one of the first-line therapies for many solid tumors with unresectable stage. However, evidence on the efficacy of ICIs in sinonasal malignancy is scarce and no ICIs are approved for use in SNSCC up to day. In this report, we report a case of a 64-year-old man with SNSCC treated by multi-protocol exploration. The patient achieved pathological complete response (pCR) after receiving two cycles of Docetaxel and cisplatin combined with tislelizumab. To the best of our knowledge, this is the first case of SNSCC treated with tislelizumab that achieved pCR. This case offers real-world evidence that chemotherapy plus immunotherapy is a promising treatment for SNSCC.