OBJECTIVE: To explore the effect of concurrent administration of goserelin for ovarian function protection on the pathological complete response (pCR) rate and objective response rate (ORR) of neoadjuvant chemotherapy (NAC) in young breast cancer patients. METHODS: The study enrolled breast cancer patients aged 18-45 with clinical stages ⅡA~ⅢC from January 2016 to May 2020. According to patients' willingness, they were divided into two groups: Those who chose to receive goserelin to protect ovarian function during NAC (goserelin group) and those who did not (chemotherapy group). The pCR rate and ORR were compared between the two groups, and subgroup analysis was conducted for patients with different molecular subtypes. RESULTS: A total of 93 patients were included in this study (31 in the goserelin group and 62 in the chemotherapy group). After propensity score weighting (PSW) adjustment, baseline data such as age, preoperative clinical stage, postoperative pathological stage, pa-thological type, hormone receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression, molecular subtypes, and chemotherapy regimens were well-matched between the two groups. There was no significant difference in the pCR rate between the goserelin group and the chemotherapy group, with rates of 29.0% and 25.8%, respectively (P=0.741). Similarly, there was no significant difference in ORR between the two groups (90.3% vs. 87.1%, P=0.746). Subgroup analysis revealed that among the patients with hormone receptor-positive tumors, there were no significant differences in pCR rate (6.3% vs. 7.7%, P=0.852) or ORR (87.5% vs. 82.1%, P=0.839) between the goserelin and chemotherapy groups. Among the patients with hormone receptor-negative tumors, there were also no significant differences in pCR rate (53.3% vs. 56.5%, P=0.847) or ORR (93.3% vs. 95.7%, P=0.975) between the two groups. One year after the completion of chemotherapy, the incidence of chemotherapy-induced amenorrhea (CIA) was significantly lower in the goserelin group compared with the chemotherapy group (9.5% vs. 33.3%, P=0.036). CONCLUSION For young breast cancer patients with clinical stages of ⅡA~ⅢC, there was no statistical difference in pCR rate and ORR whether or not using goserelin during NAC. However, it is still necessary to expand the sample size and carry out a longer follow-up to evaluate the effect of goserelin on the long-term survival of young patients.
Humans ; Goserelin/administration & dosage* ; Female ; Breast Neoplasms/pathology* ; Neoadjuvant Therapy/methods* ; Adult ; Middle Aged ; Young Adult ; Adolescent ; Chemotherapy, Adjuvant ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Treatment Outcome ; Receptor, ErbB-2

Humans ; Tumor Lysis Syndrome/drug therapy* ; Leukemia, Myeloid, Acute/pathology* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Antineoplastic Agents/therapeutic use*

OBJECTIVE: To investigate the efficacy of chemotherapy combined with antivirals in adult T-cell leukemia/lymphoma (ATLL) patients and the prognostic factors. METHODS: Forty nine patients with previously treated or treatment-nave ATLL from January 2018 to January 2021 were included in our study. The patients were divied into two groups according to whether they received antiviral treatment, twenty-seven patients were treated with chemotherapy combined with antivirals, including thirteen patients treated with recombinant interferon alpha-2b and CHOP therapy, eight patients treated with zidovudine combined with CHOP therapy, and 6 patients treated with CHOP regimen combined with interferon and zidovudine. Twenty-two patients were treated with CHOP therapy. The changes of symptom, hematological parameters, lactic dehydrogenase, β2-microglobulin, and the Ki-67 positive rate were compared between the two groups before and after treatments. The clinical efficacy of chemotherapy combined with antiviral therapy for ATLL was evaluated. The antiviral effect was assessed by detecting HTLV-1 virus copy number, and prognostic factors were analyzed. RESULTS: The median follow-up time was 14 months. Compared with the patients treated with chemotherapy alone, the patients treated with chemotherapy combined with antivirals had lower tumor and virus loads, lower white blood cell count, lower lactate dehydrogenase level, lower β2-microglobulin lever, and lower Ki-67 positive rate (all P<0.05). The total effective rate of patients treated with chemotherapy combined with antivirals was significantly higher than those of patients treated with chemotherapy alone (63.0% vs 31.8%, P=0.035). The one-year overall survival (OS) rates of chemotherapy combined with antivirals groups and chemotherapy alone group were (74.1±2.9)％ and (40.9±2.1)％ (P=0.021), respectively. The one-year progress free survival (PFS) rates were (51.9±3.3)％ and (13.6±2.8)％ (P=0.017), respectively. Multivariable Cox regression analysis showed that HTLV-1 virus load (HR=7.518, 95%CI: 2.517-36.192, P=0.013) and antiviral therapy ［HR=5.617 (95%CI 1.803-11.293), P=0.027］ were independent prognostic factors for the long-term efficacy. CONCLUSION Addition of antivirals to chemotherapy can prolong PFS and OS in ATLL patients. HTLV-1 virus load and antiviral therapy are independent prognostic factors for ATLL patients.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Antiviral Agents/therapeutic use* ; Cyclophosphamide ; Doxorubicin ; Humans ; Interferon alpha-2/therapeutic use* ; Ki-67 Antigen ; Lactate Dehydrogenases ; Leukemia-Lymphoma, Adult T-Cell/drug therapy* ; Lymphoma/drug therapy* ; Oxidoreductases/therapeutic use* ; Vincristine/therapeutic use* ; Zidovudine/therapeutic use*

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Dexamethasone/therapeutic use* ; Humans ; Multiple Myeloma/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Proto-Oncogene Proteins c-bcl-2

Objective: The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors. Methods: Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses. Results: The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ. Conclusion The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors
Animals ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation/radiation effects* ; Combined Modality Therapy ; Cytokines/immunology* ; Fatty Acids, Unsaturated/therapeutic use* ; Female ; Mammary Neoplasms, Experimental/radiotherapy* ; Rats ; Tumor-Associated Macrophages/radiation effects*

BACKGROUND: In the era of precision medicine, chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations. How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring. This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy (HCT) for advanced patients with non-small cell lung cancer (NSCLC), especially those with malignant pleural effusion. METHODS: We retrospectively evaluated medical records of 93 patients with advanced NSCLC (stage IIIB-IV) from March 2011 to January 2014. The patients were divided into HCT and chemotherapy (CT) groups. The HCT group was treated with gemcitabine and cisplatin (GP) regimen combined with regional radiofrequency deep hyperthermia, while the CT group was treated with GP regimen only. Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not. Clinical treatment results and adverse reactions were compared and analyzed after treatment. SPSS 19.0 software (SPSS Inc., USA) was used for statistical data processing. P values less than 0.05 were accepted to be statistically significant. RESULTS: Among the 93 patients, HCT group included 48 patients (16 patients with malignant pleural effusion), CT group included 45 patients (10 patients with malignant pleural effusion). There was no significant difference between the two groups in patient characteristics. The overall response rate (ORR) of pleural effusions was much better in HCT group than that in CT group (81.2% vs. 40.0%, P = 0.046). The patients in HCT group had lower incidence rate of weakness (12.5% vs. 46.7%, χ = 13.16, P < 0.001) and gastrointestinal (25.0% vs. 77.8%, χ = 25.88, P < 0.001) adverse reactions than that in CT group. The objective tumor response and survival showed no significant differences. CONCLUSIONS Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients. Also, it could greatly reduce the chemotherapy toxic effects in the incidence of weakness and gastrointestinal adverse reactions in advanced NSCLC patients.
Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; therapy ; Cisplatin ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Hyperthermia, Induced ; methods ; Lung Neoplasms ; drug therapy ; therapy ; Male ; Middle Aged ; Retrospective Studies

Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer (mCRPC). However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen (PSA) and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Adjuvant ; Docetaxel/therapeutic use* ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Neoadjuvant Therapy ; Prostatic Neoplasms/surgery* ; Taxoids/therapeutic use*

The aim of the present study was to determine whether oncologic outcomes and adverse events associated with active on/off intermittent antiandrogen monotherapy (daily bicalutamide, 50 mg per day) are comparable with those of standard external beam radiation therapy (EBRT) or combined androgen blockade (CAB) therapy in prostate cancers with positive surgical margins after radical prostatectomy. Two hundred twenty-three patients with positive surgical margins post-radical prostatectomy who underwent active surveillance (AS, n = 32), EBRT without hormone therapy (n = 55), intermittent antiandrogen monotherapy without EBRT (IAAM, n = 50), or CAB without EBRT (n = 86), between 2007 and 2014, were reviewed retrospectively. Pathologic outcomes, biochemical recurrence rates, radiological disease progression, and adverse events were collected from medical records. Biochemical recurrence rates, biochemical recurrence-free survival rates, and radiological recurrence were not different between the groups (P = 0.225, 0.896, and 0.284, respectively). Adverse event rates and severities were lower for IAAM compared with EBRT or CAB (both P < 0.05), but were comparable to those for AS (P = 0.591 and 0.990, respectively). Grade ≥3 adverse events were not reported in the IAAM or AS groups. Erectile dysfunction and loss of libido rates were lower in the IAAM group compared with the EBRT and CAB groups (P = 0.032). Gastrointestinal complications were more frequently reported in the EBRT group (P = 0.008). Active on/off IAAM treatment might be an appropriate treatment option for patients with positive surgical margins after radical prostatectomy. Furthermore, regarding oncologic outcomes, IAAM was comparable to standard EBRT but had a milder adverse event profile.
Aged ; Aged, 80 and over ; Androgen Antagonists/adverse effects* ; Anilides/adverse effects* ; Antineoplastic Agents/adverse effects* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Adjuvant/adverse effects* ; Disease-Free Survival ; Humans ; Male ; Neoplasm Recurrence, Local/blood* ; Neoplasm, Residual ; Nitriles/adverse effects* ; Prostate-Specific Antigen/blood* ; Prostatectomy ; Prostatic Neoplasms/therapy* ; Radiotherapy, Adjuvant/adverse effects* ; Retrospective Studies ; Tosyl Compounds/adverse effects*

Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response. However, several late-stage clinical trials are underway with other vaccines in prostate cancer. Reports of clinical benefit with immunotherapies, particularly when used in combination or a select population, have provided the framework to develop sound clinical trials. Understanding immunogenic modulation, antigen spread, biomarkers, and DNA-repair defects will also help mold future strategies. Through rational patient selection and evidence-based combination approaches, patients with prostate cancer may soon derive durable survival benefits with immunotherapies.
Animals ; Antineoplastic Agents, Immunological/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; B7-H1 Antigen/antagonists & inhibitors* ; Benzamides ; CTLA-4 Antigen/antagonists & inhibitors* ; Cancer Vaccines/therapeutic use* ; Humans ; Immunotherapy ; Ipilimumab/therapeutic use* ; Male ; Nitriles ; Phenylthiohydantoin/analogs & derivatives* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Prostatic Neoplasms/drug therapy* ; Tissue Extracts/administration & dosage*