The Atypical Presentation of Ifosfamide-Induced Renal Tubular Acidosis.

Antineoplastic agents are often associated with a wide range of side effects, caused by either direct toxicity or indirect through their metabolism. Ifosfamide is a cytotoxic, antineoplastic medication that is known to cause a direct tubular injury with an associated normal anion gap metabolic acidosis due to type 1 or type 2 renal tubular acidosis (RTA). The manifestations and approach to its diagnosis have been well established. However, we present a case in which a patient presented with acute symptomatic hypokalemia in the setting of ongoing ifosfamide use for metastatic osteosarcoma but without the typical laboratory findings. The clinical- and laboratory-driven diagnosis of suspected type 3 renal tubular acidosis involving proximal and distal segments is suggested by this case report.

Progress in histology specific treatments in soft tissue sarcoma.

INTRODUCTION: Soft tissue sarcomas (STS) represent a heterogenous group of rare tumors, primarily treated with surgery. Preoperative radiotherapy is often recommended for extremity high-risk STS. Neoadjuvant chemotherapy, typically based on doxorubicin with ifosfamide, has shown efficacy in limbs and trunk wall STS. Second-line chemotherapy, commonly utilized in the metastatic setting, is mostly histology-driven. Molecular targeted agents are used across various histologies, and although the use of immunotherapy in STS is still in its early stages, there is increasing interest in exploring its potential. AREAS COVERED: This article involved an extensive recent search on PubMed. It explored the current treatment landscape for localized and metastatic STS, focusing on the combined use of radiotherapy and chemotherapy for both extremity and retroperitoneal tumors, and with a particular emphasis on the most innovative histopathology driven therapeutic approaches. Additionally, ongoing clinical trials identified via clinicaltrials.gov are included. EXPERT OPINION: Recently there have been advancements in the treatment of STS, largely driven by the outcomes of clinical trials. However further research is imperative to comprehend the effect of chemotherapy, targeted therapy and immunotherapy in various STS, as well as to identify biomarkers able to predict which patients are most likely to benefit from these treatments.

Modified SMILE (mSMILE) is active in the treatment of pediatric Epstein-Barr virus-associated natural killer/T-cell lymphoma: a single center experience, case series.

Background: The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes. Methods: In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle. Results: Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy. Conclusions: Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.

A rare case of a young man with mediastinal synovial sarcoma.

Synovial sarcoma is a rare and aggressive tumor that primarily affects soft tissues, including the mediastinum, and predominantly affects younger adults. A 23-year-old male patient with mediastinal synovial sarcoma underwent debulking surgery and received 3 cycles of doxorubicin, ifosfamide, and mesna chemotherapy. Mediastinal synovial sarcoma presents diagnostic challenges and poor prognosis. Treatment involves surgical resection, adjuvant chemotherapy, and radiotherapy. Mediastinal synovial sarcoma can be diagnosed through histopathological and immunohistochemical examination. Adjuvant chemotherapy led to a partial response, showing a decrease in tumor size and resolution of pleural effusion, demonstrating a positive interim outcome.

Long term survival in adult osteosarcoma patients treated with a two-drug regimen: Final results of the OSAD93 phase II study of the FSG-GETO.

RATIONALE: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. PATIENTS AND METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. CONCLUSION: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.

Fanconi syndrome with karyomegalic interstitial nephritis after ifosfamide treatment for osteosarcoma: a case report.

Patients with ifosfamide-induced renal damage present with Fanconi syndrome. Karyomegalic nephropathy/interstitial nephritis (KNIN) is a rare form of chronic tubulo-interstitial nephritis that was initially considered a type of familial nephropathy. However, several reports of drug-induced KNIN, i.e., KNIN-like nephropathy, have been reported in recent years. We present the case of an 18-year-old man who presented with Fanconi syndrome and progressive renal dysfunction after receiving chemotherapy including ifosfamide and cisplatin for right femoral osteosarcoma. Renal biopsy revealed numerous atrophied tubular epithelial cells with large, polymorphic nuclei, and the definitive diagnosis was KNIN. Most patients with KNIN-like nephropathy who receive ifosfamide are concomitantly treated with cisplatin, indicating that ifosfamide and cisplatin might act synergistically to increase the risk for KNIN-like nephropathy. Further investigation in case series is warranted to reveal potential treatment approaches and to evaluate prognosis.

Paclitaxel-Ifosfamide-based Therapy as Salvage Treatment in Platinum-resistant Recurrent/Metastatic Head and Neck Cancer.

BACKGROUND: Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy and safety of a paclitaxel and ifosfamide (TI) regimen in patients with R/M HNSCC whose disease had progressed following platinum-based therapy. PATIENTS AND METHODS: In this retrospective study, we included 53 patients with R/M HNSCC who underwent at least one cycle of TI-based therapy, post platinum failure, between February 2020 and August 2023. Some patients received the TI regimen in combination with immunotherapy and/or cetuximab. Key metrics assessed included the objective response rate (ORR), disease control rate, and progression-free as well as overall survival. RESULTS: The study observed an ORR of 15.8% and a disease control rate of 36.8%. The median progression-free survival for the entire cohort was 3.3 months, and the median overall survival was 9.6 months. Notably, the combination of TI with immunotherapy yielded a higher ORR of 30.8%, compared to 14.3% with TI alone. The most prevalent grade 1-2 adverse events were anemia (81%), weight loss (68%) and hypernatremia (55%). CONCLUSION: The TI-based regimen demonstrated favorable efficacy and safety profile in treating R/M HNSCC. Enhanced outcomes may be attainable when combining it with immunotherapy. This study suggests that TI-based therapy could serve as a potential salvage option for this specific patient group.

Prolonged 14-day continuous infusion of high-dose ifosfamide for patients with relapsed and refractory high-grade osteosarcoma: a retrospective multicentre cohort study.

BACKGROUND: The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting. PATIENTS AND METHODS: The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5. RESULTS: The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities. CONCLUSIONS: 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.

Rare Cardiac Tumor: Do We Know All About Cardiac Myxofibrosarcoma?

Primary cardiac tumors (PCTs) are less frequent and carry an incidence of 1.38 per 100,000 population per year. Myxofibrosarcomas are reported as one of the rarest forms of cardiac sarcomas, mostly with mesenchymal origin and located in the left atrium. Current research indicates an increase in median survival from 14 months to 36 months following complete resection and chemoradiotherapy. A 55-year-old Caucasian woman was admitted with brief self-resolving episodes of aphasia following migraine headaches for the past few months with associated exertional dyspnea and episodes of hypotension. Examination revealed a right-sided facial droop with cardiac murmur on auscultation. MRI brain was recommended which revealed a non-hemorrhagic infarct and multiple watershed infarcts. A transesophageal echocardiography revealed a large mass of around 5 cm in size located at the posterior wall of the left atrium causing mitral stenosis. The patient was initially managed conservatively and referred to cardiothoracic surgery and underwent a complete surgical resection. The histopathological report indicated the presence of primary cardiac sarcoma, and a postoperative positron emission therapy (PET) scan revealed no other foci of cancer further strengthening evidence of a primary cardiac pathology. This case represents a rare cardiac pathology presenting with non-cardiac symptoms.

A Rare Case of Methemoglobinemia after Ifosfamide Infusion in a 3-Year-Old Patient Treated for T-ALL.

Methemoglobinemia is a potentially life-threatening, rare condition in which the oxygen-carrying capacity of hemoglobin is diminished. We present the case of a 3-year-old boy treated for T-cell acute lymphoblastic leukemia (T-ALL) who developed methemoglobinemia (MetHb 57.1%) as a side effect of ifosfamide administration. Due to his critical condition, the patient was transferred to the intensive care unit (ICU). The therapy included methylene blue administration, an exchange transfusion, catecholamine infusion, and steroids. Improving the general condition allowed for continuing chemotherapy without ifosfamide and completion of the HR2 block. Vigilance for methemoglobinemia as a very rare side effect should be widespread when using ifosfamide in the treatment protocols.

The Capacity of Drug-Metabolising Enzymes in Modulating the Therapeutic Efficacy of Drugs to Treat Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5-8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients. While survival rates for this childhood cancer have considerably improved over the last few decades for low-risk and intermediate-risk cases, the mortality rate remains exceptionally high in high-risk RMS patients with recurrent and/or metastatic disease. The intensification of chemotherapeutic protocols in advanced-stage RMS has historically induced aggravated toxicity with only very modest therapeutic gain. In this review, we critically analyse what has been achieved so far in RMS therapy and provide insight into how a diverse group of drug-metabolising enzymes (DMEs) possess the capacity to modify the clinical efficacy of chemotherapy. We provide suggestions for new therapeutic strategies that exploit the presence of DMEs for prodrug activation, targeted chemotherapy that does not rely on DMEs, and RMS-molecular-subtype-targeted therapies that have the potential to enter clinical evaluation.

Renal toxicity of ifosfamide in children with cancer: an exploratory study integrating aldehyde dehydrogenase enzymatic activity data and a wide-array urinary metabolomics approach.

BACKGROUND: Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity. METHODS: The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified. RESULTS: The 15 participants received a median total ifosfamide dose of 59 g/m2 (range: 24-102), given over a median of 7 cycles (range: 4-14). All children had acute proximal tubular toxicity during chemotherapy that was reversible post-cycle, seen with both conventional assays and NMR. After a median follow-up of 31 months, 8/13 children presented overall chronic toxicity among which 7 had decreased glomerular filtration rate. ALDH enzymatic activity showed high inter- and intra-individual variations across cycles, though overall activity looked lower in children who subsequently developed chronic nephrotoxicity. Concentrations of ifosfamide and metabolites were similar in all children. CONCLUSIONS: Acute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.

Rare Delayed Ifosfamide Encephalopathy: A Case Report of Chemotherapeutic Neurotoxicity.

Introduction: Neurotoxicity is a well-documented side effect of ifosfamide chemotherapy. The presentation includes hallucinations, seizures, disorientation, coma, and death. Treatment with methylene blue can shorten the duration and severity of symptoms. Ifosfamide neurotoxicity almost always happens during or shortly after drug infusion and so is usually immediately recognized. Here, we describe a case of ifosfamide neurotoxicity with onset 14 days after treatment started. Case Presentation: A 25-year-old woman with round cell sarcoma of the jaw presented to the emergency department with 2 days of encephalopathy and bizarre behavior. Antipsychotic medications and benzodiazepines produced no benefit. After consultation, oncology recommended methylene blue, hypothesizing that her symptoms could be a rare presentation of delayed ifosfamide-induced neurotoxicity, 14 days after first administration. After 4 days of methylene blue infusion, her functioning returned to baseline. Conclusion: Delayed ifosfamide-related neurotoxicity is a rare side effect of this chemotherapeutic agent and should be considered in the workup of altered mental status, even if symptoms occur after the previously accepted 5-day standard. In such patients, delayed symptomology may require extended use of methylene blue as treatment.

Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against MCF-7 and A549 Cells.

Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-α was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 µM and 10 µg/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-α and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments.

Cytoreductive Surgery with Bidirectional Intraoperative Chemotherapy (BDIC) Using Intravenous Ifosfamide Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Peritoneal Sarcomatosis: A Retrospective Cohort Study.

BACKGROUND: Peritoneal sarcomatosis (PS) is a rare tumor with limited therapeutic options. Bidirectional intraoperative chemotherapy (BDIC) using intravenous ifosfamide and doxorubicin-based hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) is an emerging treatment for peritoneal malignancies. PATIENTS AND METHODS: Patients with PS who underwent CRS/BDIC using intravenous ifosfamide and HIPEC from January 2017 to July 2021 were retrospectively analyzed. The last follow-up date was May 2022. RESULTS: A total of 29 patients were included. Overall survival (OS) rates at 6, 12, 24, and 48 months after CRS/BDIC were 93.1%, 89.2%, 81.4%, and 73.3%, respectively. As of May 2022, 6 patients (20.6%) had died, including four (13.8%) with a proven recurrent tumor and two with incomplete tumor resection [completeness of cytoreduction (CC)-2 or CC-3]. Of the 20 patients (68.9%) with CC-0 or CC-1, 7 had locoregional tumor recurrence without distant metastasis, whereas the other 13 were alive with no evidence of recurrent tumor in May 2022. Disease recurrence rates were 15% at 6 months and 35% at 12, 24, and 48 months after CRS/BDIC. Clavien-Dindo class ≥ IIIa complications developed in 9 patients (31.0%) with no deaths. Leukopenia occurred in 5 patients (17.2%) and thrombocytopenia in 12 patients (41.3%); these hematologic abnormalities resolved. A total of 9 (31.0%) patients developed nephrotoxicity; all recovered except one, who progressed to chronic kidney disease. CONCLUSIONS: CRS/BDIC using intravenous ifosfamide and doxorubicin-based HIPEC is a potentially effective treatment for PS and has an acceptable rate of complications.

Volatile anticancer drug determination by thermal desorption technique with polydimethylsiloxane-coated macroporous silica adsorbent in gas chromatography-mass spectrometry.

An analytical method for quantifying the volatile anticancer drugs ifosfamide (IF) and cyclophosphamide (CP) in air was developed on the basis of thermal desorption (TD)-gas chromatography-mass spectrometry. Polydimethylsiloxane-coated macroporous silica was used as the adsorbent. The extraction tube was prepared by packing 0.2 g of adsorbent particles into a glass tube. The extraction and desorption efficiencies of the proposed method were quantitatively investigated in this study. The limits of detection of the proposed method for IF and CP were 3.3 ng L-1 at an air sampling volume of 3.0 L (30 min). The sensitivity of the proposed method was compared with using a Tenax TA packed tube that is widely used as the extraction medium in TD analysis. Finally, detection of IF and CP that evaporated from aqueous standard solution was investigated.

Ifosfamide-induced nephrotoxicity in oncological patients.

INTRODUCTION: Ifosfamide is an alkylating chemotherapeutic agent used in the treatment of various neoplasms. Its main adverse effects include renal damage. AREAS COVERED: A comprehensive review was conducted, including 100 articles from the Scielo, Scopus, and EMBASE databases. Ifosfamide-induced nephrotoxicity is attributed to its toxic metabolites, such as acrolein and chloroacetaldehyde, which cause mitochondrial damage and oxidative stress in renal tubular cells. Literature review found a 29-year average age with no gender predominance and a mortality of 13%. Currently, no fully effective strategy exists for preventing ifosfamide-induced nephrotoxicity; however, hydration, forced diuresis, and other interventions are employed to limit renal damage. Long-term renal function monitoring is essential for patients treated with ifosfamide. EXPERT OPINION: Ifosfamide remains essential in neoplasm treatment, but nephrotoxicity, often compounded by coadministered drugs, poses diagnostic challenges. Preventive strategies are lacking, necessitating further research. Identifying timely risk factors can mitigate renal damage, and a multidisciplinary approach manages established nephrotoxicity. Emerging therapies may reduce ifosfamide induced nephrotoxicity.

Ifosfamide is a type of chemotherapy used to treat different types of cancers. However, one of its main side effects is kidney damage. Researchers reviewed 100 articles from medical databases to understand how ifosfamide affects the kidneys. The kidney damage is caused by harmful substances produced when ifosfamide is broken down in the body. These substances can harm the cells in the kidneys. Studies have shown that 13% of the patients treated with ifosfamide can die. Currently, there is no perfect way to prevent kidney damage from ifosfamide, but doctors try to protect the kidneys by giving patients plenty of fluids and using other treatments, so it's important for patients who receive ifosfamide to have their kidney function checked regularly. Although ifosfamide is effective against cancer, its potential kidney side effects should be carefully considered by doctors when deciding on the best treatment for each patient.

In vivo hepatoprotective and nephroprotective effects of Stenocarpus sinuatus leaf extract against ifosfamide-induced toxicity in rats.

Ifosfamide (IFOS) is a broad-spectrum chemotherapeutic agent that has been extensively used for breast cancer and other solid tumors. Unfortunately, its use is associated with toxicities of several organs. Stenocarpus sinuatus is an Australian tree belonging to the Proteaceae family. In the current study, the phytochemical constituents of S. sinuatus methanol leaf extract (SSLE) were assessed. In addition, the protective effect of SSLE against IFOS-induced nephrotoxicity and hepatotoxicity was evaluated. Rats were randomly divided into six groups: control, IFOS (50 mg/kg), IFOS + SSLE (100 mg/kg), IFOS + SSLE (200 mg/kg), IFOS + SSLE (400 mg/kg), and SSLE (400 mg/kg). Hepatoprotective and nephroprotective potency of SSLE was assessed using different biochemical parameters. The phytochemical investigation resulted in the isolation of four flavonoid glycosides (kaempferol 3-O-ß- d-glucopyranosyl-(1→2)-α- l-rhamnopyranoside, kaempferol 3-O-α-rhamnopyranoside, isorhamnetin 3-O-ß- d-glucopyranosyl-(1→2)-α- l-rhamnopyranoside, and quercetin 3-O-ß- d-glucopyranosyl-(1→2)-α- l-rhamnopyranoside) and a coumarin (scopoletin). This is the first report on the isolated compounds from the genus Stenocarpus. SSLE showed enhancement of kidney and liver functions and reduction of oxidative stress and inflammation. The histopathology of the investigated organs confirmed the protective effect of SSLE. In conclusion, SSLE is considered as a promising candidate that can be used in defense against the toxic effects of IFOS after further clinical trials.

Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma.

Purpose: Uterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma. Materials and methods: This is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen. Results: Fifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events. Conclusion: Use of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma.

Pre- and post-chemotherapy spermatogenesis in male patients with malignant bone and soft tissue tumors.

Introduction: Malignant bone and soft tissue tumors, commonly called sarcomas, predominantly originate in bone and soft tissues and typically affect individuals at a younger age. Following the resection of the primary tumor, treatment often necessitates radiation therapy and gonadotoxic chemotherapy, the specifics of which depend on the disease's stage Conversely, there is a notable concern regarding the potential loss of fertility due to these treatments. Consequently, it is recommended that men consider sperm cryopreservation before initiating treatment. This study aims to assess spermatogenesis in male patients diagnosed with malignant bone and soft tissue tumors before and after chemotherapy. Methods: This study involved 34 male patients diagnosed with malignant bone and soft tissue tumors and subsequently underwent sperm cryopreservation before initiating treatment. Medical records included details about the primary disease, age, marital status at presentation, semen analysis results, treatment regimen and number of courses, post-treatment semen analysis, renewal status and outcomes. Results: The mean age at the time of sperm cryopreservation was 22.8 years. The median semen volume was 2.5 mL, sperm concentration was 32.6 million/ml, and sperm motility was 38.5%. Following chemotherapy, semen analysis was conducted on 12 patients, with ifosfamide being the predominant drug used in all cases. Among these 12 patients, eight retained viable spermatozoa, and two successfully achieved spontaneous pregnancies resulting in live births. In one of the remaining four cases where no sperm were detected in ejaculate, a live birth was achieved through intracytoplasmic sperm injection using cryopreserved sperm. Discussion: While ifosfamide, the primary chemotherapy drug for patients with malignant bone and soft tissue tumors, was associated with severe impairments in spermatogenesis, recovery of spermatogenesis was observed in many cases. However, there were instances of prolonged azoospermia. Even in such cases, assisted reproduction using cryopreserved sperm remained viable for achieving parenthood. In light of these findings, offering patients the opportunity for fertility preservation is advisable.