Docetaxel Chemotherapy Research Articles

P103-9 Partial response to docetaxel and gemcitabine chemotherapy in a patient with HG-ESS stage IV: a case report

P103-9 Partial response to docetaxel and gemcitabine chemotherapy in a patient with HG-ESS stage IV: a case report

Weekly versus 2-weekly versus 3-weekly docetaxel to treat metastatic castration-resistant prostate cancer

BackgroundTo compare the efficacy and toxicity of docetaxel treatment regimens in metastatic castration-resistant prostate cancer (mCRPC). MethodsWe retrospectively analyzed 162 patients diagnosed with mCRPC who underwent docetaxel chemotherapy between 2009 and 2020. The subjects were divided into three groups according to the dosage and interval of docetaxel (DCT) chemotherapy regimen: 30 mL/m2 weekly, 50 mL/m2 2-weekly (every 2 weeks), and 75 mL/m2 3-weekly (every 3 weeks). ResultsThere were no significant differences in the prostate specific antigen (PSA) response rates (p = 0.709). The median time to progression was 3.0 (IQR 2.0-5.3) months, 5.0 (IQR 2.0-13.0) months, and 5.0 (IQR 3.0-12.0) months in the weekly, biweekly, and triweekly groups, respectively (p = 0.062). The median overall survival (OS) was 12.5 (IQR 6.0-14.0) months, 18.8 (IQR 5.5-23.5) months, and 22.9 (IQR 11.0-33.0) months in the weekly, biweekly, and triweekly groups, respectively (p < 0.001). There were no differences in all toxicity and grade 3 or higher toxicity. In Cox multivariate regression analysis, the Eastern Cooperative Oncology Group performance status (ECOG-PS), response to chemotherapy, and chemotherapy cycle also affected the PFS. Age, ECOG-PS and chemotherapy cycle affected the OS. ConclusionsThe various options for optimal chemotherapy are indicated depending on the patient's conditions during the diagnosis of mCRPC. Treatment with DCT at 2-week or even 1-week intervals appears to be well tolerated in men diagnosed with mCRPC and represents a useful option when the conventional triweekly regimen is not tolerated due to poor patient condition.

Clinical utility of pegfilgrastim on day 3 of preoperative docetaxel, cisplatin and 5-fluorouracil chemotherapy in elderly patients with resectable esophageal cancer

Clinical utility of pegfilgrastim on day 3 of preoperative docetaxel, cisplatin and 5-fluorouracil chemotherapy in elderly patients with resectable esophageal cancer

The efficacy of gemcitabine and docetaxel chemotherapy for the treatment of relapsed and refractory osteosarcoma: A systematic review and pre-clinical study.

Osteosarcoma is the most common primary malignancy of the bone. There is a lack of effective treatments for patients who experience relapsed osteosarcoma. One treatment for relapsed patients is gemcitabine and docetaxel combination chemotherapy (GEMDOX). This systematic review aimed to establish the efficacy of this chemotherapy regimen, as well as identify the common severe toxicities that are associated with it. Resistant osteosarcoma cell lines developed from MG-63 and HOS-143B were used to represent relapsed osteosarcoma patients in a pre-clinical study. We identified 11 retrospective and Phase II studies that were suitable for inclusion in our review. 10.65% of patients had a response to gemcitabine and docetaxel combination therapy and the disease control rate was 35% (n = 197). 36%, 35.3% and 18.04% of patients experienced grade 3 or 4 neutropenia, thrombocytopenia and anaemia respectively (n = 133). Male patients (X2 = 9.14, p < 0.05) and those below the age of 18 (X 2 = 10.94, p < 0.05) responded better to GEMDOX treatment than females and patients older than 18 years. The resistant osteosarcoma cell lines remained sensitive to either single-agent gemcitabine, docetaxel, and the combination of both. Cisplatin-resistant models (MG-63/CISR8 & HOS-143B/CISR8) were the most responsive to GEMDOX treatment compared to doxorubicin, methotrexate, and triple-combination resistant models. GEMDOX treatment has potential efficacy in relapsed osteosarcoma patients especially those with cisplatin resistance. To directly compare the efficacy of GEMDOX therapy against other therapies randomised phase III clinical trials with adequate patient follow up must be performed to improve treatment options for osteosarcoma.

Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer.

Metabolic reprogramming and cellular senescence greatly contribute to cancer relapse and recurrence. In aging and treated prostate, persistent accumulating senescence-associated secretory phenotype (SASP) of cancer cells often limits the overall survival of patients. Novel strategic therapy with monoacylglycerol lipase (MGLL) upregulation that counters the cellular and docetaxel induced SASP might overcome this clinical challenge in prostate cancer (PCa). With primary comparative expression and survival analysis screening of fatty acid (FA) metabolism signature genes in the TCGA PCa dataset and our single center cohort, MGLL was detected to be downregulated in malignancy prostate tissues and its low expression predicted worse progression-free and overall survival. Functionally, overexpression of MGLL mainly suppresses NF-κB-driven SASP (N-SASP) which mostly restricts the cancer cell paracrine and autocrine tumorigenic manners and the corresponding cellular senescence. Further investigating metabolites, we determined that MGLL constitutive expression prevents lipid accumulation, decreases metabolites preferably, and consequently downregulates ATP levels. Overexpressed MGLL inhibited IκBα phosphorylation, NF-κB p65 phosphorylation, and NF-κB nuclear translocation to deactivate NF-κB transcriptional activities, and be responsible for the repressed N-SASP, partially through reducing ATP levels. Preclinically, combinational treatment with MGLL overexpression and docetaxel chemotherapy dramatically delays tumor progression in mouse models. Taken together, our findings identify MGLL as a switch for lipase-related N-SASP suppression and provide a potential drug candidate for promoting docetaxel efficacy in PCa.

Contemporary treatment standards and trends of systemic therapy in metastatic hormone-sensitive prostate cancer-implementing study data in clinical practice

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has undergone fundamental changes in recent decades, moving away from the sole use of androgen deprivation therapy (ADT) and towards intensified combination therapies. To what extent have the data from prospective phaseIII studies influenced clinical practice in the management of mHSPC over the past 5 or 10years? Atotal of 1098 mHSPC patients with amedian age at metastasis of 70years and amedian prostate-specific antigen (PSA) level of 43 ng/ml were included in the present study. Significant differences were observed in terms of PSA nadirs in mHSPC after stratification by year of metastatic onset. Significant differences were also observed regarding systemic therapies applied in mHSPC and metastatic castration-resistant prostate cancer (mCRPC; p < 0.001). Regarding the annual estimated percentage change (EAPC) over the past 10years, asignificant decrease in ADT monotherapy from 85% (2013) to 29% (2023; EAPC: -12%, p < 0.001) was observed. Conversely, there was asignificant increase in androgen receptor signaling inhibitor (ARSI) use from 6% in 2013 to 55% in 2023 (EAPC: +21.7%, p < 0.001). Regarding docetaxel chemotherapy, abell-shaped pattern was apparent over the past 10years, with rates increasing from 8% in 2013 to 25% in 2019 and decreasing to 0% in 2023. The proportion of triplet therapies was 16% in 2023. Over the past 10years there has been an adaptation of intensified combination therapies for mHSPC in clinical reality, with the most frequent use of ARSI and triplet therapies.

Mecapegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia in locally advanced nasopharyngeal carcinoma: A prospective phase II clinical study.

Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen. A total of 30 treatment-naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24-48 h after the completion of induction chemotherapy with the TP regimen. The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%-22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%-17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles. Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.

4-Cholesten-3-one Modified the Lipidome of MDA-MB-231 Cells and Potentiated the Effect of Docetaxel.

Lipids are essential for energy production, signaling, and membrane formation, hence increased lipid metabolism may lead to cancer growth. 4-cholesten-3-one (4Cone), a sterol metabolite, has various biological activities, including the inhibition of cancer growth. This study examined whether 4Cone could change the lipid profile of triple-negative breast cancer cells (MDA-MB-231) and whether in combination with the anti-cancer chemotherapy docetaxel (TXT) could further reduce cancer aggressiveness. The effect of 4Cone, TXT, or their combination (4Cone/TXT) on migration and proliferation was examined utilizing the wound healing and MTT assays. The expression of the lipogenesis-related enzymes was assessed using RT-qPCR and lipid profile was examined using mass spectrometry. 4Cone and TXT individually reduced cell viability and migration of MDA-MB-231 cancer cells; however, their combination (4Cone/TXT) had a greater impact on both attributes. All treated cells showed markedly decreased levels of the multidrug resistance enzyme PGP as well as the lipogenic enzymes FASN, ACC1, SCD1, HMGCR, and DGAT. Furthermore, lipid fingerprints were markedly different in treated cells compared with the untreated group. 4Cone increased the percentage of sphingomyelin (SM) while it decreased the percentage of ceramide (Cer); 4Cone in conjunction with TXT had the reverse effect. Triglyceride levels were reduced in 4Cone- and 4Cone/TXT-treated cells, but interestingly, they increased in TXT-treated cells. Additionally, treated cancer cells exhibited changes in glycerophospholipid subclasses. 4Cone alone or in combination with TXT alters the lipid profile by reducing a key lipogenic enzyme, resulting in the inhibition of cell proliferation and migration.

Bicalutamide Enhances Conventional Chemotherapy in In Vitro and In Vivo Assays Using Human and Canine Inflammatory Mammary Cancer Cell Lines.

Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are highly aggressive neoplastic diseases that share numerous characteristics. In IBC and IMC, chemotherapy produces a limited pathological response and anti-androgen therapies have been of interest for breast cancer treatment. Therefore, the aim was to evaluate the effect of a therapy based on bicalutamide, a non-steroidal anti-androgen, with doxorubicin and docetaxel chemotherapy on cell proliferation, migration, tumor growth, and steroid-hormone secretion. An IMC-TN cell line, IPC-366, and an IBC-TN cell line, SUM149, were used. In vitro assays revealed that SUM149 exhibited greater sensitivity, reducing cell viability and migration with all tested drugs. In contrast, IPC-366 exhibited only significant in vitro reductions with docetaxel as a single agent or in different combinations. Decreased estrogen levels reduced in vitro tumor growth in both IMC and IBC. Curiously, doxorubicin resulted in low efficacy, especially in IMC. In addition, all drugs reduced the tumor volume in IBC and IMC by increasing intratumoral testosterone (T) levels, which have been related with reduced tumor progression. In conclusion, the addition of bicalutamide to doxorubicin and docetaxel combinations may represent a potential treatment for IMC and IBC.

Assessing the impact of MSH3 and MSH6 polymorphisms on lung cancer risk in North Indian patients undergoing platinum chemotherapy through molecular dynamics simulation

The present study investigated the relationship between MSH3 and MSH6 genes in lung cancer patients. Genotyping of lung cancer patients and healthy controls was performed. Odds ratio values were calculated and survival analysis performed. Patients with mutant genotype (TT) for MSH6 polymorphism have 1.5-fold risk for the development of lung cancer (p = 0.03). For non-smokers, the mutant-type genotype had a threefold increased risk of lung cancer (p = 0.01). Patients administered with docetaxel and carbo/cisplatin and carrying GT genotype for MSH6 polymorphism, patients reported a decrease in median survival time (4.9 vs 9.13 months). MSH3 and MSH6 polymorphisms are involved in modulating the risk towards lung cancer. MSH6 polymorphism is associated with high mortality rate for patients undergoing cisplatin and docetaxel chemotherapy.

The impact of androgen deprivation therapy on bone microarchitecture in men with prostate cancer: A longitudinal observational study (The ANTELOPE Study)

IntroductionAndrogen Deprivation Therapy (ADT) for prostate cancer (PC) has substantial negative impacts on the musculoskeletal system and body composition. Many studies have focused on the effects of ADT on areal bone mineral density (aBMD), but aBMD does not capture key determinants of bone strength and fracture risk, for example volumetric bone density (vBMD), geometry, cortical thickness and porosity, trabecular parameters and rate of remodelling. More specialist imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) have become available to evaluate these parameters. Although it has previously been demonstrated that bone microarchitectural deterioration occurs in men undergoing ADT, the aim of the ANTELOPE study was to examine longitudinal changes in bone microstructure alongside a range of musculoskeletal parameters and frailty, comparing men with PC receiving ADT alone or ADT plus chemotherapy for metastatic disease, with a healthy age-matched population. MethodsWe used HR-pQCT to investigate effects of 12 months of ADT on vBMD and microstructural parameters, complemented by assessment of changes in aBMD, serum bone turnover markers, sex hormones, body composition, grip strength, physical and muscle function, frailty and fracture risk. We studied three groups: Group A − men with localised/locally advanced PC due to commence ADT; Group B − men with newly diagnosed hormone-sensitive, metastatic PC, starting ADT alongside docetaxel chemotherapy and steroids; Group C − healthy, age-matched men. The primary endpoint was change in vBMD (Group A vs Group C) at the distal radius. ResultsNinety-nine participants underwent baseline study assessments (Group A: n = 38, Group B: n = 30 and Group C: n = 31). Seventy-five participants completed all study assessments (Group A (29), Group B (18), Group C (28). At baseline, there were no significant differences between Groups A and C in any of the BMD or bone microstructure outcomes of interest. After 12 months of ADT treatment, there was a significantly greater decrease in vBMD (p < 0.001) in Group A (mean 12-month change = -13.7 mg HA/cm3, −4.1 %) compared to Group C (mean 12-month change = -1.3 mg HA/cm3, −0.4 %), demonstrating achievement of primary outcome. Similar effects were observed when comparing the change in vBMD between Group B (mean 12-month change = -13.5 mg HA/cm3, −4.3 %) and Group C. These changes were mirrored in aBMD. ADT resulted in microstructural deterioration, a reduction in estimated bone strength and an increase in bone turnover. There was evidence of increase in total fat mass and trunkal fat mass in ADT-treated patients, with marked loss in upper limb mass, along with BMI gain. Frailty increased and physical performance and strength deteriorated in both ADT groups, relative to the healthy control group. ConclusionThe study showed that ADT has profound effects on vBMD, aBMD, bone microstructure and strength and body composition, and important impacts on frailty and physical performance. Whilst DXA remains a valuable tool (changes in aBMD are of the same magnitude as those observed for vBMD), HR-pQCT should be considered for assessing the effects of anti-androgens and other newer PC therapies on bone, as well as potential mitigation by bone-targeted agents.

Docetaxel plus cis-platinum chemotherapy for the posterior line treatment of metastatic castrate-resistant prostate cancer with elevated neuron specific enolase.

e17042 Background: This Study is to figure out the efficacy of docetaxel plus cis-platinum (DC) chemotherapy as the posterior line treatment for metastatic castrate-resistant prostate cancer (mCRPC) with elevated neuron specific enolase (NSE). Methods: We performed a retrospective study of men suffered mCRPC with elevated NSE from December 2019 to August 2022. All men were treated with DC after resistance to previous therapy. Biochemical progression-free survival (BPFS) were depicted using Kaplan-Meier curves. Results: 10 mCRPC patients aged 65.8 ± 7.0 (Median: 66.5, Range: 52-77) received DC for 1 to 10 cycles (Median: 7). Of the 10 patients, 2, 1 and 7 patients underwent DC as the 2nd, 3rd and 4th line therapy, respectively. 3 patients received previous chemotherapy and 9 patients underwent new endocrine therapy. All patients suffered bone metastases, 6 patients suffered distal lymph node metastases and 3 patients suffered visceral metastases. 6.1 ± 2.8 cycles (Median: 7, Range: 1-10) of DC were finished. Median follow-up time was 6.5 (Range: 2-11) months. After DC, Prostate specific antigen (PSA) response rate (&gt;50%) was 90% and NSE response rate (&gt;50%) was 60%. Median BPFS was 10 (Range: 4-18) months. Pain score declined from 6.6 ± 3.1 to 3.9 ± 2.4 evidently (P &lt; 0.05) and Karnofsky (KPS) score increased from 80 ± 14.9 to 91 ± 16.0 significantly (P &lt; 0.05). Of the 6 patients assessed by radiological examinations, 5 patients experienced partial response and 1patient achieved stable disease. Conclusions: Our pilot study showed docetaxel plus cis-platinum chemotherapy was effective for the mCRPC patients with elevated NSE resistant to multi-line therapies, indicating the potential value of DC for mCRPC with neuroendocrine differentiation.

4CAST: A phase 1b dose exploration, open-label, single-center study evaluating the safety of INO-464 in combination with chemotherapy in patients with metastatic breast cancer.

e13112 Background: Metastatic triple negative breast cancer (TNBC) has a poor prognosis and the development of new targeted therapies is an area of unmet need. The androgen receptor (AR) antagonist, INO-464, but not abiraterone or enzalutamide, blocks chemotherapy induced cell plasticity to inhibit and primary and metastatic breast cancer (MBC) growth. Single agent INO-464 at a dose of 450mg/d is well tolerated but has low efficacy. Laboratory data demonstrates suppression of metastatic TNBC and an increase in survival with the combination of INO-464 and taxane chemotherapy. Methods: We designed a Phase 1b open-label, single center dose exploration (Part 1) and dose expansion (Part 2) clinical trial of INO-464 450mg/d with docetaxel (IV 75mg/m2 q3wkly) or nab-paclitaxel (IV 100mg/m2 D1/8/15 q4wkly) in any subtype of MBC. The primary objective was to assess the safety and tolerability of INO-464 (450mg/d) and docetaxel or nab-paclitaxel utilizing a rolling 6 design, as well as to determine the maximum tolerated dose (MTD) and the recommended dose of INO-464 to be given with a taxane in the dose expansion study. Secondary objectives included anti-tumor activity and testosterone levels. Results: Recruitment began in August 2022. The cut-off date for this analysis was 19 January 2024. Eight patients have been treated to date and 6 patients were DLT evaluable. All were women with MBC with mean age of 56 (range 48-64) years. Patients had received a median of 5 (range 2 to 7) lines of chemotherapy for MBC. Patient 001 had G3 anaphylaxis due to docetaxel that resolved with adrenaline but came off study and was not DLT evaluable. The protocol was amended to give INO-464 with 1mg of dexamethasone. No DLTs were subsequently observed. Adverse events (AEs) were mostly low grade and chemotherapy related although G2 pneumonitis occurred beyond the DLT period in two patients, one of whom had prior sacituzimab govotecan-related pneumonitis. INO-464-related AEs were G1 fatigue/headache in 4/6 patients. Seven of seven patients had a best response (RECIST1.1) SD, and CA15.3 stability was seen in 4/7 patients. Baseline serum testosterone was detectable in 4/6 patients (range 0.5-1.3 nmol/L, lower limit of detection of &lt;0.5), and remained undetectable or at the lower limit of detection throughout treatment. Conclusions: The MTD of INO-464 is 450mg daily with 0.5mg dexamethasone in combination with docetaxel or nab-paclitaxel chemotherapy. The combination is well tolerated with early efficacy signals. Dose expansion will test the combination in metastatic TNBC with nuclear AR positive breast cancer. Clinical trial information: NCT04947189 .

Analysis of effectiveness of FLOT perioperative chemotherapy in resectable locally advanced gastric or esophago-gastric junction cancer in a Kazakhstani population.

e16129 Background: Gastric cancer is the third most common malignancy in Kazakhstan and the second leading cause of cancer-related mortality. Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) perioperative chemotherapy is widely accepted treatment strategy of locally advanced gastric adenocarcinoma in Western countries. However, radical surgery is a preferable approach in Kazakhstan. The objective of this study was to assess the effectiveness and feasibility of FLOT perioperative chemotherapy in curable locally advanced gastric or esophago-gastric junction cancer. Methods: In this study, we reviewed the retrospective data of patients with locally advanced gastric or esophago-gastric junction cancer, who received FLOT perioperative chemotherapy between January 2020 and December 2022 in single center. To evaluate the effectiveness of treatment, histopathological regression, disease free survival (DFS) and 1- and 3-year overall survival outcomes were analyzed. Results: Total 136 patients with stage II and III with gastric or esophago-gastric junction cancer were treated. Fifty-six patients (41%) received FLOT preoperative chemotherapy. 9% (5) patients couldn’t complete all cycles of chemotherapy due to serious adverse events. Disease progression was observed in 10 (19%) patients after FLOT preoperative chemotherapy. Of the 46 radically operated patients, 5 (11%) had complete or near complete pathology response, 33 (72%) patients had partial response, and 8 (17%) patients had no response for preoperative chemotherapy (p = 0,405). 7 patients had not get adjuvant chemotherapy. Overall, 1- and 3-year survival were 78,6% and 34,9% respectively, disease free survival was 76,8% and 39% respectively. Conclusions: The FLOT perioperative chemotherapy was effective and feasible to administer and might be a standard treatment option among patients with locally advanced gastric or esophago-gastric junction cancer.

Pulmonary blastoma with a good prognosis: a case report and review of the literature.

Pulmonary blastoma (PB) is a rare, highly malignant tumor prone to distant metastasis and recurrence, and the prognosis of these patients is often poor. We report a case of metastatic PB with a good prognosis with the aim of providing data to support a clinical diagnosis and treatment. In December 2015, a 43-year-old male patient was admitted to our hospital because of a cough and blood-stained sputum. Positron emission-computed tomography showed massive high-density imaging in the lower lobe of the right lung, with a maximum cross-section of 76 × 58 mm. Thoracoscopic-assisted right lower lobectomy with lymph node dissection was performed. After 1 month, computed tomography showed a high possibility of metastasis. The patient then received docetaxel and cisplatin chemotherapy for a total of six courses. After chemotherapy, enhanced computed tomography showed considerable absorption of pleural effusion, and a left lobe pulmonary nodule was not detected. The postoperative pathological diagnosis was PB, and epithelial and mesenchymal differentiation components were observed. The patient continued to visit the hospital regularly for re-examination and imaging examinations. Currently, no signs of recurrence or distant metastasis have been detected.

Treatment of metastatic hormone-sensitive prostate cancer: from doublet therapy to triplet therapy.

For metastatic prostate cancer, androgen deprivation therapy (ADT) is the key strategy to control the disease. However, after 18-24months of treatment, most patients will progress from metastatic hormone-sensitive prostate cancer (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC) even with ADT. Once patients enter into mCRPC, they face with significant declines in quality of life and a dramatically reduced survival period. Thus, doublet therapy, which combines ADT with new hormone therapy (NHT) or ADT with docetaxel chemotherapy, substitutes ADT alone and has become the "gold standard" for the treatment of mHSPC. In recent years, triplet therapy, which combines ADT with NHT and docetaxel chemotherapy, has also achieved impressive effects in mHSPC. This article provides a comprehensive review of the recent applications of the triplet therapy in the field of mHSPC.

Cancer associated fibroblast secreted miR-432-5p targets CHAC1 to inhibit ferroptosis and promote acquired chemoresistance in prostate cancer.

Prostate cancer (PCa) ranks as the sixth most serious male malignant disease globally. While docetaxel (DTX) chemotherapy is the standard treatment for advanced PCa patients with distant metastasis, some individuals exhibit insensitivity or resistance to DTX. Cancer-associated fibroblasts (CAFs) play a pivotal role as stromal cells within the tumor microenvironment, influencing tumor development, progression, and drug resistance through exosomes. Ferroptosis, a novel form of programmed cell death, is characterized by intracellular iron accumulation that triggers lipid peroxidation, ultimately leading to cell demise. To delve into the potential mechanisms of chemotherapy resistance in prostate cancer, our research delved into the impact of CAF-derived exosomes on ferroptosis. Our findings revealed that CAF exosomes hindered the buildup of lipid reactive oxygen species (ROS) in prostate cancer cells induced by erastin, as well as mitigated erastin-induced mitochondrial damage, thereby impeding iron-induced cell death in prostate cancer cells. Furthermore, miR-432-5p was identified to diminish glutathione (GSH) consumption by targeting CHAC1, consequently inhibiting ferroptosis in prostate cancer cells. Our study found that miR-432-5p, originating from cancer-associated fibroblast (CAF) exosomes, suppresses ferroptosis by targeting CHAC1, thereby increasing resistance to docetaxel (DTX) in PCa. This research introduces a novel approach to address resistance to DTX.

Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols.

The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG(Bacillus Calmette-Guérin) treatment in non-muscleinvasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baselinecharacteristics, riskgroup stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan-Meier survival analysis was performed to detect Recurrence-free survival (RFS). Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66-79), and a median follow-up time of 18months (IQR 9-25), were included. Forty-one hadan intermediate-risk disease (49%) and 42 hada high-risk disease (51%). Thirty-sevenpatients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6months 88% vs 100%, at 12months 71% vs 97%, at 18months 57% vs 91%, and at 24months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2g Gemcitabine with Docetaxel had better RFS for all-graderecurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.

THE ROLE OF DOCETAXEL AS FIRST-LINE CHEMOTHERAPY ON PSA LEVEL AND QOL IN CRPC PATIENTS

Objective: Prostate cancer is the second most common cancer in men and the fifth leading cause of death worldwide. 10-20% of cases can progress to a more aggressive stage called castration-resistant prostate cancer (CRPC) with a higher death rate. Clinical guidelines recommend docetaxel as first-line chemotherapy and evaluated using the PSA test. This study aims to investigate the effect of docetaxel chemotherapy on PSA levels in CRPC. Material &amp; Methods: A retrospective study was conducted from January 2016 until August 2022 according to the medical records database Saiful Anwar Hospital. There were 16 patients who met the inclusion criteria, including male patients with a diagnosis of CRPC who received castration therapy and found an increase in PSA 3 times of nadir or found 2 or more bone metastatic lesions or soft tissue lesions &gt; 2 cm, received 6 series of docetaxel chemotherapy, and have a PSA data was performed before and after chemotherapy. Statistical analysis was performed using a differential T-test. Results: The results, obtained were significantly different (p&lt;0.05) on the average PSA (log) pre-post chemotherapy, visual analog scale (VAS), and quality of life, and not significantly different on BMI pre-post chemotherapy. Conclusion: 6 cycles of docetaxel chemotherapy resulted in a decrease in PSA levels of CRPC significantly. It showed an excellent response to docetaxel chemotherapy in managing CRPC patients. Limitations of this study were specifically the retrospective cohort study model and the ability to reduce PSA levels in assessing the prognosis of CRPC. Keywords: Castration-resistant prostate cancer, chemotherapy, docetaxel, prostate-specific antigen.

Abstract PS16-07: Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy

Abstract Background: Stromal tumor-infiltrating lymphocytes (sTILs) quantification is associated with pathological response to neoadjuvant chemotherapy (NAC) and long term outcomes in setting of adjuvant anthracycline based chemotherapy. A previous study in TNBC patients treated with adjuvant anthracycline chemotherapy shows that at a cut point of 30%, sTILs can up and downstage traditional AJCC stage groups. Additive impact of sTILs on refining outcomes beyond pathological response and TNM stage for patients treated with anthracycline-free chemotherapy is not known. This study aimed to investigate impact of sTILs on outcomes in a large cohort of TNBC patients treated with Docetaxel plus carboplatin NAC. Methods: Patients with stage I (T size &amp;gt; 1cm) to III TNBC scheduled to receive 6 cycles of NAC docetaxel (75 mg/m2) plus carboplatin (AUC 6) (TCb) every 3 weeks from two studies (NCT01560663 and NCT02302742) were combined for this analysis. sTILs were evaluated on pre-treatment H&amp;E slide using standard criteria centrally by one of the investigators (RS). Pathological complete response (pCR) was defined as ypT0/is ypN0. Logistic regression analysis was used to examine the effect of multiple variables on Event free survival (EFS) and overall survival (OS). Results: For 474 patients included in this analysis, median age was 52 years, 8% were Black, 13% had germline BRCA1/2 mutation, 44% had clinical Lymph node (LN) positive disease and 13%, 62% and 25% respectively had TNM stage I, II and III disease. Median sTILs were 5% (range 1-95%) and 25% had &amp;gt;30% sTILs. pCR and RCB 0+1 rates were 50.2% and 60.4% respectively. On multivariable analysis, T stage (OR=0.51, p=0.030), nodal status (OR=0.56, p=0.028), Ki67 (OR=2.74, p&amp;lt; 0.001) and sTILs (OR=2.01, p=0.014) were associated with pCR. pCR rate in those with sTILs &amp;lt; 30 vs sTILs &amp;gt;30 was 45.9% and 63.9% respectively (p=0.0014). At median follow-up of 58 months, 5 years EFS was 81.05% in all patients, 93.94% in those with pCR and 68.67% in those without pCR, 5 year OS was 84.83% in all patients, 96.53% in those with pCR and 74.13% in those with residual disease. On multivariate analysis lower T stage, negative LN status and increasing sTILS were associated with better EFS (T stage: HR =1.98, p=0.018; LN status: HR=2.92, p&amp;lt; 0.001; sTILs: HR:0.46, p=0.04) and OS (T stage: HR=1.89, p=0.040; LN status: HR=3.13, p=0.001; sTILs: HR=0.30, p=0.008). At a cut-point of 30%, sTILs up and downstaged anatomic AJCC TNM stage groups (table 1). Conclusions and Relevance: In patients treated with anthracycline-free TCb chemotherapy, sTILs were independent predictors of EFS and OS beyond clinicopathological features. Notably, 30% sTILs cut-point stratified outcomes beyond anatomical TNM staging. These, findings can aid in patient stratification for chemotherapy backbone de-escalation in future trials and have the potential to inform patient selection for adjuvant treatment escalation and de-escalation trials. Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy. Table. Citation Format: Miguel Martín, Rachel Yoder, Roberto Salgado, María del Monte-Millán, Enrique Álvarez, Isabel Echavarria, Joshua Staley, Coralia Bueno-Muiño, Yolanda Jerez Gilarranz, Andrew Godwin, María Cebollero, Oscar Bueno, José Ángel García-Sáenz, Fernando Moreno Antón, Uriel Bohn, Henry L Gómez, Tatiana Massarrah, Sara López-Tarruella, Priyanka Sharma. Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-07.