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Cureus Aug 2023Standard whole-brain radiotherapy (WBRT) alone for large brain metastases (BMs) from small cell lung cancer (SCLC) has limited efficacy and durability, and stereotactic...
Standard whole-brain radiotherapy (WBRT) alone for large brain metastases (BMs) from small cell lung cancer (SCLC) has limited efficacy and durability, and stereotactic radiosurgery (SRS) alone for symptomatic posterior fossa BMs >3 cm with satellite lesions is challenging. Herein, we describe the case of a 73-year-old female presenting with treatment-naïve SCLC and 15 symptomatic multiple BMs, including a ≥3.8-cm cerebellar mass (≥17.7 cm) and two adjacent lesions; otherwise, the SCLC was confined to the thorax. The patient was initially treated concurrently with conventional WBRT (30 Gy in 10 fractions) without boost and chemoimmunotherapy (CIT) consisting of carboplatin, etoposide, and atezolizumab. Atezolizumab was excluded during irradiation. Five months after WBRT, the large cerebellar lesion had remarkably regressed, and the smaller lesions (≤17 mm) showed complete responses (CRs) without local progression at 20 months. However, six and 16 months after WBRT, the thoracic lesions had progressed, and although amrubicin was administered, four new BMs, including pons involvement, had developed, respectively. Despite the CRs of the four BMs following SRS (49.6 Gy in eight fractions) and the sustained regression of the thoracic lesions, meningeal dissemination and multiple new BMs were evident 3.5 months post-SRS. The small remnant of the large BM and/or newly developed BMs abutting the cerebrospinal fluid (CSF) space could have led to CSF dissemination, the presumed cause of the patient's death. Taken together, concurrent chemo-WBRT and subsequent CIT can provide excellent and durable tumor responses for SCLC BMs, but may not be fully sufficient for BMs ≥3.8 cm. Therefore, in cases with large lesions, focal dose escalation of the large lesions, consolidative thoracic radiotherapy, and dose de-escalation in the macroscopically unaffected brain region may prevent or attenuate CSF dissemination, new BM development, and adverse effects and thus should be considered.
PubMed: 37727186
DOI: 10.7759/cureus.43759 -
Anticancer Research Sep 2023Neuroendocrine prostate cancer (NEPC) is generally an aggressive form of prostate cancer that can arise de novo or develop as a castration-resistant mechanism. While... (Review)
Review
Neuroendocrine prostate cancer (NEPC) is generally an aggressive form of prostate cancer that can arise de novo or develop as a castration-resistant mechanism. While first-line platinum-based chemotherapy is effective against NEPC, its limited response duration and subsequent treatments pose significant clinical challenges. Standard second-line treatments have not been established due to the limited data available. The aim of this review was to reveal the current status of second-line therapy for NEPC. A literature search was conducted using PubMed and Web of Science and a total of 13 articles were included in this review. Prospective and retrospective studies demonstrated that treatment outcome of second-line therapy using platinum with etoposide or docetaxel was unfavorable and progression-free survival was 3 months or shorter. Amrubicin and irinotecan were also frequently used as second-line therapy, however, efficacy of these agents was modest and response duration was less than 6 months. NEPC patients with homologous recombination repair gene alterations may benefit from treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. Ongoing clinical studies investigate various agents, including immune checkpoint inhibitors, molecularly targeted agents, and PARP inhibitors. With the increasing recognition and active biopsy of NEPC lesions, the number of NEPC patients is anticipated to rise. Accumulating more knowledge and experience is crucial in developing novel treatment strategies to combat this disease.
Topics: Male; Humans; Prospective Studies; Retrospective Studies; Prostatic Neoplasms; Prostate; Docetaxel
PubMed: 37648316
DOI: 10.21873/anticanres.16571 -
Cureus Apr 2023A 64-year-old man was referred from a local clinic with a chief complaint of cough. Computed tomography (CT) revealed a mass comprising a tumor in the right lower lobe...
A 64-year-old man was referred from a local clinic with a chief complaint of cough. Computed tomography (CT) revealed a mass comprising a tumor in the right lower lobe and enlarged mediastinal lymph nodes, and a whole-body workup with positron emission tomography-CT showed bilateral lymph node enlargement and cancerous pericarditis. Biopsy with bronchoscopy of the right lower lobe tumor and mediastinal lymph node confirmed the histological findings of small cell lung carcinoma. The clinical diagnosis of extensive-stage small cell lung cancer (ES-SCLC) was confirmed, and first-line treatment with carboplatin, etoposide, and atezolizumab was initiated, followed by tri-weekly atezolizumab thrice. The patient experienced worsening pleural effusion treated with thoracentesis, pleural drainage, and pleurodesis. He also experienced several recurrences, which were managed with second and third-line chemotherapy with nogitecan and amrubicin. He has been receiving third-line therapy for over 30 months since his initial visit and remains stable as of today. The patient experienced an exceptional treatment outcome considering that the prognosis of ES-SCLC remains poor, with a median survival of approximately 10 months with conventional chemotherapies using cytotoxic agents. The use of immune checkpoint inhibitors (ICI) for ES-SCLC as first-line treatment may demonstrate a persistent antitumor effect, and result in improved survival following discontinuation. In conclusion, therapy including ICI for patients with ES-SCLC is a treatment option that shows possibilities in improving survival even after discontinuation.
PubMed: 37213944
DOI: 10.7759/cureus.37757 -
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 -
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 -
Frontiers in Oncology 2023It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.
Comparison of the second-line treatments for patients with small cell lung cancer sensitive to previous platinum-based chemotherapy: A systematic review and Bayesian network analysis.
OBJECTIVE
It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.
METHODS
We systematically screened randomized controlled trials from several online databases. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and hematological complications graded 3 to 5. The efficacy of included treatments was ranked by surface under the cumulative ranking curve (SUCRA) value.
RESULTS
We included eleven trials involving 1560 patients in quantitative analysis. Triple chemotherapy containing platinum (TP, combination of cisplatin, etoposide, and irinotecan) was associated with favorable ORR (intravenous topotecan vs TP; odds ratio: 0.13, 95% CI:0.03-0.63; SUCRA, 0.94) and PFS (vs intravenous topotecan; hazard ratio, 0.5; 95% CI: 0.25-0.99; SUCRA, 0.90). Belotecan ranked highest for OS (SUCRA, 0.90), while intravenous topotecan plus Ziv-aflibercept ranked highest for DCR (SUCRA, 0.75). TP was more likely to cause anemia and thrombocytopenia while intravenous topotecan plus Ziv-aflibercept resulted in most neutrocytopenia.
CONCLUSION
TP is the first recommendation for the second-line treatment of sensitive relapsed SCLC. TP achieved priority in ORR and PFS with the most frequent adverse effects in anemia and thrombocytopenia. For patients who cannot tolerate the hematological adverse effects of triple chemotherapy, amrubicin is an optional option. Amrubicin had relatively good ORR and PFS, accompanied by fewer hematological complications. The rechallenge of the platinum doublet is inferior to amrubicin in ORR, DCR, and PFS. Oral topotecan has a similar effect compared with IV topotecan, but oral topotecan was associated with slightly higher safety and less stress in nursing. Belotecan contributed to the best PFS with slightly better safety but was not ideal in other outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358256.
PubMed: 37007093
DOI: 10.3389/fonc.2023.1154685 -
Thoracic Cancer May 2023Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in...
BACKGROUND
Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy.
METHODS
The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group).
RESULTS
The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001).
CONCLUSIONS
In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Retrospective Studies; Neoplasm Recurrence, Local; Disease Progression; Antineoplastic Agents; Treatment Outcome
PubMed: 36994539
DOI: 10.1111/1759-7714.14871 -
Japanese Journal of Clinical Oncology Jun 2023This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell...
Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.
OBJECTIVE
This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer.
METHODS
We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival.
RESULTS
The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis.
CONCLUSION
Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.
Topics: Male; Humans; Cisplatin; Etoposide; Carboplatin; Lung Neoplasms; Retrospective Studies; Small Cell Lung Carcinoma; Treatment Outcome; Prostatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36828781
DOI: 10.1093/jjco/hyad011 -
Thoracic Cancer Jan 2023The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however,...
Clinical efficacy of amrubicin in patients with small cell lung cancer relapse after first-line treatment including immune checkpoint inhibitors: A retrospective multicenter study (TOPGAN 2021-01).
BACKGROUND
The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however, it is unclear whether the same is applicable for small cell lung cancer (SCLC). We evaluated the efficacy of second-line amrubicin (AMR) following first-line platinum-based chemotherapy and ICI combination therapy (chemo-ICI) in SCLC.
PATIENTS AND METHODS
We retrospectively enrolled consecutive patients with SCLC treated with AMR as a second-line following chemo-ICI as first-line between July 2019 and April 2021 from 16 institutions throughout Japan. We investigated the therapeutic effectiveness, safety, and efficacy-enhancing variables of AMR.
RESULTS
Overall, 89 patients treated with AMR after first-line chemo-ICI were analyzed. The overall response rate (ORR) was 29.2% (95% confidence intervals [CI], 20.1-39.8) and median PFS (m PFS) was 2.99 months (95% CI, 2.27-3.65). Patients who relapsed more than 90 days after receiving first-line platinum combination therapy (sensitive relapse) exhibited greater ORR (58.3% vs. 24.7%, p = 0.035) and m PFS (5.03 vs. 2.56 months, p = 0.019) than patients who relapsed in <90 days (refractory relapse). Grade 3 or higher adverse events were mainly hematological toxicity.
CONCLUSIONS
Our study suggested that the therapeutic effect of AMR was not enhanced after ICI on SCLC. However, AMR may be effective in cases of sensitive relapse after chemo-ICI. There was no increase in severe toxicity associated with AMR after ICI.
Topics: Humans; Lung Neoplasms; Immune Checkpoint Inhibitors; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Neoplasm Recurrence, Local; Small Cell Lung Carcinoma; Antineoplastic Agents; Treatment Outcome; Recurrence
PubMed: 36408699
DOI: 10.1111/1759-7714.14729 -
IJU Case Reports Nov 2022Small-cell carcinoma of the prostate has a poor prognosis, and treatment options for the refractory disease are unclear.
INTRODUCTION
Small-cell carcinoma of the prostate has a poor prognosis, and treatment options for the refractory disease are unclear.
CASE PRESENTATION
A 68-year-old man with prostate cancer was referred to our hospital. He was treated with combined androgen blockade (bicalutamide and degarelix acetate). The disease progressed to castration-resistant prostate cancer, but with additional treatment, prostate-specific antigen levels remained below 0.02 ng/mL. However, computed tomography revealed enlarged right inguinal lymph nodes; moreover, his neuron-specific enolase levels were elevated. Histopathologic analysis of a biopsied lymph node confirmed small-cell carcinoma. After administering cytotoxic chemotherapy (etoposide plus cisplatin and amrubicin), the patient temporarily improved before relapsing. After genetic testing of the biopsy specimen revealed a deletion, we administered the oral PARP-2 inhibitor olaparib, which has achieved partial remission for 8 months.
CONCLUSION
PARP-2 inhibition may improve the survival of patients with -positive small-cell carcinoma of the prostate.
PubMed: 36341199
DOI: 10.1002/iju5.12523