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Chemotherapy 2022Data on the clinical outcomes of patients receiving adjuvant chemotherapy for surgically resected high-grade pulmonary neuroendocrine carcinoma (HGNEC) (large-cell...
INTRODUCTION
Data on the clinical outcomes of patients receiving adjuvant chemotherapy for surgically resected high-grade pulmonary neuroendocrine carcinoma (HGNEC) (large-cell neuroendocrine carcinoma and small-cell lung cancer) are limited. This study aimed to evaluate the prognostic significance of adjuvant chemotherapy in patients with HGNEC.
METHODS
We retrospectively analyzed patients with surgically resected HGNEC at five institutions in Japan between January 2006 and May 2016.
RESULTS
A total of 143 patients were enrolled. Among them, 65 received adjuvant chemotherapy. Four patients who participated in clinical trials were excluded; the remaining 61 patients were included in the study. Fifty-six patients received adjuvant small-cell lung cancer-based chemotherapy. Twenty-five of 29 patients who relapsed after postoperative adjuvant chemotherapy received chemotherapy. The most commonly administered chemotherapy agent was amrubicin. The 3-year relapse-free and overall survival rates were 55.2% and 66.8%, respectively. The median relapse-free and overall survival times for the 25 patients who received chemotherapy after relapse were 12.9 and 27.5 months, respectively. Among them, 22 relapsed within 2 years. Patients who received platinum-doublet chemotherapy after relapse tended to have better time to progression disease and overall survival than those who received single-agent chemotherapy.
CONCLUSIONS
Most patients with HGNEC received small-cell lung cancer-based regimens as postoperative adjuvant chemotherapy. Those who relapsed after adjuvant chemotherapy were mainly treated with amrubicin. Our findings suggest that platinum-doublet chemotherapy tends to improve the time to progression disease and overall survival in patients who relapse after postoperative adjuvant chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Chemotherapy, Adjuvant; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Platinum; Retrospective Studies; Small Cell Lung Carcinoma
PubMed: 35313303
DOI: 10.1159/000524077 -
Journal of Rural Medicine : JRM Oct 2021The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate...
The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy. We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital. The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18-51), and 112 days (95% CI = 55-267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections. The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.
PubMed: 34707735
DOI: 10.2185/jrm.2021-014 -
International Journal of Oncology Mar 2020Squamous cell lung carcinoma (SQCLC) is an aggressive type of lung cancer. In contrast with the marked advances that have been achieved in the treatment of lung...
Histone deacetylase inhibitor OBP‑801 and amrubicin synergistically inhibit the growth of squamous cell lung carcinoma by inducing mitochondrial ASK1‑dependent apoptosis.
Squamous cell lung carcinoma (SQCLC) is an aggressive type of lung cancer. In contrast with the marked advances that have been achieved in the treatment of lung adenocarcinoma, there are currently no effective targeted therapies for SQCLC, for with cytotoxic drugs are still the main treatment strategy. Therefore, the present study aimed to develop novel combination therapies for SQCLC. The results demonstrated that a combined treatment with the potent histone deacetylase (HDAC) inhibitor OBP‑801 and the third‑generation anthracycline amrubicin synergistically inhibited the viability of SQCLC cell lines by inducing apoptosis signal‑regulating kinase 1 (ASK1)‑dependent, as well as JNK‑ and p38 mitogen‑activated protein kinase (MAPK)‑independent apoptosis. OBP‑801 treatment strongly induced the protein expression levels of thioredoxin‑interacting protein (TXNIP), and amrubicin treatment increased the levels of intracellular reactive oxygen species (ROS), which suggested that this combination oxidized and dissociated thioredoxin 2 (Trx2) from mitochondrial ASK1 and activated ASK1. Moreover, mouse xenograft experiments using human H520 SQCLC cells revealed that the co‑treatment potently suppressed tumor growth in vivo. These results suggested that a combined treatment with OBP‑801 and amrubicin may have potential as a therapeutic strategy for SQCLC.
Topics: Animals; Anthracyclines; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Histone Deacetylase Inhibitors; Humans; Lung Neoplasms; MAP Kinase Kinase Kinase 5; Mice; Peptides, Cyclic; Xenograft Model Antitumor Assays
PubMed: 32124968
DOI: 10.3892/ijo.2020.4969 -
Thoracic Cancer Aug 2022Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable...
Phase I study of amrubicin plus cisplatin and concurrent accelerated hyperfractionated thoracic radiotherapy for limited-disease small cell lung cancer: protocol of ACIST study.
BACKGROUND
Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited-disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non-inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive-disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD-SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of AP in patients with LD-SCLC.
METHODS
Treatment-naive patients with LD-SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m /day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m /day. RD and MTD will be determined by evaluating toxicities.
DISCUSSION
Based on our previous study, the initial dose of AMR 25 mg/m is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD-SCLC.
Topics: Adult; Aged; Anthracyclines; Chemoradiotherapy; Cisplatin; Clinical Trials, Phase I as Topic; Etoposide; Humans; Lung Neoplasms; Middle Aged; Small Cell Lung Carcinoma; Young Adult
PubMed: 35808894
DOI: 10.1111/1759-7714.14555 -
Gan To Kagaku Ryoho. Cancer &... Apr 2023We analyzed 4 cases who experienced extravasation of anthracyclines and had dexrazoxane therapy in our hospital. Concerned drugs were 2 adriamycin and 2 amrubicin cases...
We analyzed 4 cases who experienced extravasation of anthracyclines and had dexrazoxane therapy in our hospital. Concerned drugs were 2 adriamycin and 2 amrubicin cases and all cases received steroid ointment therapy, and no cases showed severe condition such as skin ulcer. As dexrazoxane is known to enhance bone marrow suppression of anti-cancer drugs, the nadir of neutropenia and thrombocytopenia was observed from day 10 to 17 in our cases. We made a domestic manual and have used in various professionals. Dexrazoxane would contribute to the reduction of skin damage due to extravasation if we could manage bone marrow suppression successfully.
Topics: Humans; Dexrazoxane; Razoxane; Antibiotics, Antineoplastic; Anthracyclines; Antineoplastic Agents
PubMed: 37066459
DOI: No ID Found -
Anticancer Research Mar 2021We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin...
BACKGROUND/AIM
We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin (AMR).
PATIENTS AND METHODS
A retrospective cohort study was conducted in patients with SCLC receiving AMR as second-line therapy.
RESULTS
A total of 33 patients were treated with AMR (no PEG group), while 13 patients were treated with AMR plus prophylactic administration of PEG (PEG group). The severity of neutropenia was significantly reduced in the PEG group compared to the no PEG group (p=0.02). The incidence of FN in the no PEG and PEG groups was 27.3% and 7.7%, respectively. The time to development of FN tended to be longer in the PEG group compared to the no PEG group (p=0.132).
CONCLUSION
Primary prophylaxis with PEG may be beneficial in reducing the risk of FN in patients with SCLC receiving AMR.
Topics: Aged; Anthracyclines; Antineoplastic Agents; Febrile Neutropenia; Female; Filgrastim; Humans; Lung Neoplasms; Male; Polyethylene Glycols; Retrospective Studies; Small Cell Lung Carcinoma
PubMed: 33788757
DOI: 10.21873/anticanres.14923 -
International Cancer Conference Journal Apr 2024Small cell carcinoma (SCC) of the urinary bladder is a rare and highly aggressive subtype of bladder cancer. Most cases are diagnosed at advanced stages, and its...
Small cell carcinoma (SCC) of the urinary bladder is a rare and highly aggressive subtype of bladder cancer. Most cases are diagnosed at advanced stages, and its therapeutic strategy remains unestablished. Here, we report a case of bladder SCC in which multidisciplinary treatment has resulted in relatively long-term survival. A 68-year-old man presented with gross hematuria. A cystoscopy revealed an invasive bladder tumor. A transurethral resection of bladder tumor (TURBT) was performed, and the pathological diagnosis was SCC. After systemic chemotherapy using etoposide and carboplatin and subsequent TURBT, a radical cystectomy and ileal conduit were performed. Three months postoperatively, the patient had a recurrence in the para-aortic lymph node. Systemic combination chemotherapy with carboplatin plus irinotecan (CBDCA + CPT-11) was administered, followed by amrubicin and an immune checkpoint inhibitor. In addition to this treatment, radiation therapy for the metastatic region led to the reduction of pain and shrinkage of the metastatic lesion. The patient survived for 2 years after the initial diagnosis. Our report indicates that multidisciplinary treatment can be effective for SCC of the bladder, and a therapeutic strategy including the identification of novel biomarkers should be established.
PubMed: 38524643
DOI: 10.1007/s13691-023-00644-4 -
International Cancer Conference Journal Jul 2020Standard therapy for metastatic small cell carcinoma of the prostate (SCCP) remains undefined. We have effectively treated relapsed SCCP with amrubicin. A 72-year-old...
Standard therapy for metastatic small cell carcinoma of the prostate (SCCP) remains undefined. We have effectively treated relapsed SCCP with amrubicin. A 72-year-old patient, diagnosed with T4N1M0 prostate cancer, started hormonal therapy in May 2012, elsewhere, and his prostate-specific antigen levels remained low. However, pulmonary and hepatic metastases occurred; high neuron-specific enolase levels suggested SCCP, which was confirmed by repeated biopsy at our institution. In October 2016, chemotherapy with irinotecan and cisplatin was initiated for metastases to the lung, liver, and left pelvic lymph nodes, and partial response (PR) was achieved. After six cycles, brain metastases occurred. After ten cycles, his pro-gastrin-releasing peptide levels increased suddenly, and brain and hepatic metastases enlarged. Amrubicin was started in December 2016 and seven cycles were safely completed, with PR and markedly reduced brain metastasis volume, until his pneumonitis-related death in June 2017. Amrubicin may be an effective second-line chemotherapy option for SCCP.
PubMed: 32582522
DOI: 10.1007/s13691-020-00416-4 -
International Journal of Clinical... Jul 2023Amrubicin (AMR) is one of the most active agents for small-cell lung cancer (SCLC). However, hematologic toxicity and infection at a commonly used dose (40 mg/m) is...
BACKGROUND
Amrubicin (AMR) is one of the most active agents for small-cell lung cancer (SCLC). However, hematologic toxicity and infection at a commonly used dose (40 mg/m) is problematic; the optimal dose remains undetermined.
PATIENTS AND METHODS
To evaluate the optimal dose of AMR in terms of efficacy and safety, we reviewed consecutive data on patients with relapsed SCLC who received AMR at doses of 40, 35, and 30 mg/m (on days 1-3) at Nippon Medical School Hospital between October 2010 and November 2021.
RESULTS
We reviewed the data of 86 patients (20, 45, 27 who received AMR doses of 40, 35, 30 mg/m, respectively) according to our study criteria. For patients ≥ 75 years, the proportion who received second-line treatment tended to be higher in the 30-35 mg/m group. Objective response rates were 37/46/35%, median progression-free survival (PFS) were 3.0/4.7/3.2 months, and median overall survival (OS) were 7.8/16.3/8.0 months, respectively. Grade 4 neutropenia occurred in 58/39/31% of patients, which was higher for the 40 mg/m group. The incidence of febrile neutropenia did not differ between groups. Multivariate analysis identified the AMR dose was not associated with longer PFS and OS.
CONCLUSION
Treatment with AMR between 30 and 35 mg/m showed relatively mild hematologic toxicity compared with AMR at 40 mg/m, without any significant difference in efficacy. Lower dose of AMR for relapsed SCLC could be a promising treatment option.
Topics: Humans; Anthracyclines; Antineoplastic Agents; Lung Neoplasms; Retrospective Studies; Small Cell Lung Carcinoma; Treatment Outcome
PubMed: 37171692
DOI: 10.1007/s10147-023-02343-9 -
In Vivo (Athens, Greece) 2020Concurrent chemoradiotherapy (CCRT) is the gold standard for limited-stage small-cell lung cancer (LS-SCLC); however, most patients inevitably experience relapse. We...
BACKGROUND
Concurrent chemoradiotherapy (CCRT) is the gold standard for limited-stage small-cell lung cancer (LS-SCLC); however, most patients inevitably experience relapse. We hypothesized consolidation amrubicin following CCRT to be a potential treatment for LS-SCLC.
PATIENTS AND METHODS
All enrolled patients were treated using induction CCRT consisting of four cycles of etoposide and cisplatin plus concurrent thoracic radiotherapy. Eligible patients then received three cycles of amrubicin as consolidation therapy (consolidation population). The primary endpoint was the 2-year progression-free survival rate in the consolidation population.
RESULTS
Of the 36 intention-to-treat patients, 28 (78%) received amrubicin and 24 (67%) completed all planned treatments. The 2-year progression-free survival rate and overall response rate were 35.7% and 86%, respectively. The median progression-free and overall survival were 14.3 and 60.9 months, respectively. There were no treatment-related deaths in the intention-to-treat population.
CONCLUSION
This study was terminated due to slow patient accrual; however, this treatment strategy was feasible and demonstrated promising efficacy.
Topics: Aged; Anthracyclines; Antineoplastic Agents; Chemoradiotherapy; Combined Modality Therapy; Consolidation Chemotherapy; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Small Cell Lung Carcinoma; Treatment Outcome
PubMed: 32111801
DOI: 10.21873/invivo.11855