scholarly journals Management of Apatinib-Related Adverse Events in Patients With Advanced Osteosarcoma From Four Prospective Trials: Chinese Sarcoma Study Group Experience

2021 ◽  
Vol 11 ◽  
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Wei Guo ◽  
Zhen Wang ◽  
Yang Yao ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kinase Inhibitors ◽  
Response Rate ◽  
High Response Rate ◽  
Consensus Meeting ◽  
Study Group ◽  
Optimal Outcomes ◽  
Treatment Benefits ◽  
Prospective Trials ◽  
Group Experience

Four prospective trials have reported apatinib-related efficacy in osteosarcoma, with a high response rate of 43.2%. Currently, Adverse Events (AEs) have increasingly gained attention, as treatment with multiple tyrosine kinase inhibitors (TKIs) is potentially lifelong. For this reason, a consensus meeting of the Chinese Sarcoma Study Group (CSSG), which is a multidisciplinary panel composed of pediatric, medical and surgical oncologists specializing in sarcoma, nurse specialists, oncological senior pharmacists and gastroenterologists, was held to develop comprehensive guidelines on AEs emerging due to apatinib treatment to better assist in the prevention, management, and understanding of AE development. We summarized all AEs that arose in ≥10% of the participants as well as rare AEs that required extra caution to prevent that were observed in these four published prospective trials and arranged these AEs into 14 disorder systems according to CTCAE 5.0. In this review, we discuss strategies for the management of AEs in patients with advanced osteosarcoma, with the aim of maximizing treatment benefits and minimizing the need for apatinib treatment discontinuation. We also focus on providing recommendations for the prophylaxis and treatment of advanced osteosarcoma using apatinib to achieve optimal outcomes.

Improving immune-related adverse event management in a thoracic clinic.

2017 ◽  
Vol 35 (8_suppl) ◽  
pp. 74-74
Author(s):  
Meghan Shea ◽  
Deepa Rangachari ◽  
Daniel Botelho Costa ◽  
Aya Sato-DiLorenzo ◽  
Jessica A. Zerillo
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
Package Insert ◽  
Retrospective Chart Review ◽  
High Response Rate ◽  
Event Management ◽  
Metastatic Nsclc ◽  
United States Food ◽  
States Food ◽  
Us Fda

74 Background: Widespread use of immunotherapeutic agents has transformed the profile of adverse events associated with systemic cancer therapy. Management of immune-related adverse events (IRAEs) is contingent upon grading severity using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Nivolumab and Pembrolizumab were recently approved for metastatic non-small cell lung cancer (NSCLC). United States Food and Drug Administration (US FDA)-approved package label inserts provide guidance on IRAE management and are predicated on CTCAE grade, including when to discontinue drug. Currently, clinicians in the thoracic oncology group are documenting CTCAE grade of IRAEs infrequently, and management is varied. Methods: A retrospective chart review of baseline data revealed 45 patients (8 on Pembrolizumab, 37 on Nivolumab) who initiated immunotherapy for metastatic NSCLC between March 2015 and August 2016. A team of clinicians developed a process map from diagnosis of IRAE to initiation of toxicity management. Physicians were surveyed. The team’s aim is by February 1, 2017, at least 50% of patients who develop an IRAE on immunotherapy for metastatic NSCLC have documentation of toxicity grade using the CTCAE criteria. Results: The physician survey response rate was 12 of 16 (75%). Physicians reported not using grade to guide management of IRAEs over two thirds (67%) of the time. Time to look up CTCAE criteria and knowing that grade is needed ranked as the top barriers. At baseline, 18 of 45 (40%) patients had 22 IRAEs, of which 6 IRAEs (27%) had grading documented; all graded IRAEs (100%) were managed according to guidelines in the drug-specific package insert. IRAEs included hypothyroidism, pneumonitis, hepatitis, dermatitis, adrenal insufficiency, colitis, and encephalitis. Conclusions: Education on toxicity grading and ease of accessibility to information regarding management of IRAEs are needed. Because clinicians were engaged, a survey to evaluate the current process succeeded with a high response rate. At baseline, there are significant gaps and variability in current practice. Interventions are underway to standardize documentation of grade and management of patients experiencing IRAEs.

scholarly journals The efficacy and adverse events of anlotinib plus PD-1 inhibitor for metastatic solid tumors

2021 ◽  
Author(s):  
Hao Lin ◽  
Tao Liu ◽  
Xinli Zhou ◽  
Xiaohua Liang
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Kinase Inhibitors ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Kaplan Meier ◽  
Hemorrhagic Events ◽  
Tumor Immune Microenvironment

Abstract Background Several antiangiogenic tyrosine kinase inhibitors (TKIs) have the potential to modulate the tumor immune microenvironment and improve immunotherapy effect Of these, anlotinib has demonstrated antitumor efficacy in clinical trials. However, its role in immune regulation and the potential synergistic antitumor effect of its combination with PD-1 inhibitor remain unclear. This study investigated the efficacy and adverse events (AEs) of the combination of anlotinib and PD-1 inhibitor for solid tumors in real-world settings. Methods This retrospective study included patients with metastatic solid tumors treated with anlotinib plus PD-1 inhibitor at Huashan hospital, Fudan University between October 1, 2018 and August 31, 2020. The objective response rate was assessed using the response evaluation criteria in solid tumors v1.1. Descriptive statistics were performed using the Kaplan–Meier method, and any AEs were noted. Results Partial response was achieved in 13 patients, and 8 patients showed stable disease, representing a response rate of 43.3% and a disease control rate of 70%. The median progression-free survival was 3.8 months. Although AEs were observed in 50% of patients, most of them were Grades 1–2 and well tolerated. The most common AEs were thrombocytopenia (16%), thromboembolic or hemorrhagic events (16%), and rash (13%). Conclusions Anlotinib plus PD-1 inhibitor is an alternative salvage treatment choice in metastatic solid tumors with Favorable efficacy and tolerable toxicities.

scholarly journals Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

2019 ◽  
Vol 3 (6) ◽  
pp. 851-861 ◽  
Author(s):  
Preetesh Jain ◽  
Hagop Kantarjian ◽  
Prajwal C. Boddu ◽  
Graciela M. Nogueras-González ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myeloid Leukemia ◽  
Regression Models ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Increased Risk ◽  
Prospective Trials ◽  
Grade 3 ◽  
New Onset

Abstract Cardiovascular or arteriothrombotic adverse events (CV- or AT-AEs) are reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). The incidence and characteristics across different TKI have not been systematically analyzed. We analyzed 531 patients treated with frontline TKIs in different prospective trials: imatinib 400 mg (n = 71) and 800 mg (n = 203), nilotinib (n = 108), dasatinib (n = 106), and ponatinib (n = 43). Characteristics and incidence of new-onset CV-AEs and AT-AEs were analyzed. Poisson regression models assessed factors associated with AE incidence. Median follow-up was 94 months (range, 2-195). Overall, 237 patients (45%) developed CV-AEs and 46 (9%) developed AT-AEs. Hypertension was the most common AE seen in 175 patients (33%; grade 3/4 in 17%). CV-AE and AT-AE incidence ratios (IRs) with 95% confidence intervals (CIs) were 8.6 (7.6-9.8) and 1.7 (1.2-2.2) per 100 person-years. Among the TKIs, ponatinib showed the highest IR (95% CI) for CV-AEs and AT-AEs at 40.7 (27.9-59.4) and 9.0 (4.1-20.1). In multivariate analysis, ponatinib therapy was associated with increased incidence rate ratio (IRR) for CV-AEs (4.62; 95% CI, 2.7-7.7; P < .0001) and AT-AEs (6.38; 95% CI, 1.8-21.8; P < .0001) compared with imatinib 400. In summary, there is an increased risk of CV-AEs (except hypertension) and AT-AEs in CML patients treated with newer TKIs, particularly with ponatinib. Patients on TKIs must be informed and closely monitored for vascular AEs. These studies were registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, #NCT00050531, #NCT00254423, #NCT00129740, and #NCT01570868.

Lenalidomide/Dexamethasone Improves Response and Prolongs Time to Progression, Even in Patients with IgA Multiple Myeloma: A Sub-Analysis of the MM-009/010 Studies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4839-4839 ◽  
Author(s):  
Robert Foa ◽  
Donna Weber ◽  
Meletios Dimopoulos ◽  
Marta Olesnyckyj ◽  
Zhinuan Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response ◽  
High Response Rate ◽  
Response To Therapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Phase Iii Trials ◽  
The Impact

Abstract Background: Historically, patients with IgA multiple myeloma (MM) respond poorly to treatment. In 2 recent phase III trials, Lenalidomide (Len) in combination with Dexamethasone (Dex) led to an overall response (OR) rate of approximately 60% (61% in MM-009 and 60% in MM-010), a complete response (CR) rate of about 15% (14% and 16%, respectively), an overall survival (OS) of at least 29.5 months (29.5 and not yet reached), and a median time to progression (TTP) of at least 11.1 months (11.1 months and 11.3 months, respectively) in patients with relapsed/refractory MM. In both studies, OR, CR, OS and TTP were significantly better with Len/Dex than with Dex alone. Here, we assess the impact of IgA disease on the efficacy and tolerability of treatment with Len/Dex versus Dex alone. Methods: Data were pooled from the MM-009 and MM-010 studies. Patients were randomized to receive Len (25 mg/day on days 1–21 of each 28-day cycle) or placebo. Both groups received Dex 40mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first four cycles). After four cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, and adverse events were assessed. Response rate and TTP were based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Results: Of 154 patients with IgA at baseline, 72 were treated with Len/Dex and 82 with Dex alone. Among those without IgA, 281 received Len/Dex and 269 received Dex alone. Baseline characteristics were balanced between treatment groups. Len/Dex was associated with a significantly higher OR and longer median TTP than Dex alone in patients with and without IgA (Table). In the non-IgA group, patients treated with Len/Dex had a significantly longer OS than those treated with Dex alone. Response, TTP and OS were comparable between IgA and non-IgA patient groups. There was no difference in the incidence of adverse events between patients with and without IgA. Among those with IgA, the most common grade 3–4 adverse events with Len/Dex and Dex alone were neutropenia (37.5% and 2.4%), thrombocytopenia (16.7% and 8.5%), and anemia (11.1% and 7.3%). The respective rates for patients without IgA were 46.5% and 14.5%, 12.1% and 5.7%, and 11.0% and 5.7%. Conclusion: In patients with and in those without IgA MM, Len/Dex treatment induces a high response rate and a prolonged TTP compared with Dex. IgA non-IgA Clinical response, % Len/Dex (n=72) Dex alone (n=82) P Len/Dex (n=281) Dex alone (n=269) P OR 68.1 18.3 <0.001 57.7 23.0 <0.001 CR 18.1 0 NS 14.2 2.6 NS PR 38.9 15.9 NS 35.6 19.3 NS Median TTP, wks 44.3 16.4 <0.001 52.1 20.1 <0.001 Median OS, wks 130.4 102.4 NS 156.0 136.1 <0.05

Reduced-Dosage of Three Drugs Combination of Cyclophosphamide, Bortezomib and Dexamethasone (reduced-CyBorD) Retains High Response Rate with Less Toxicities in Elderly Patients with Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1865-1865 ◽  
Author(s):  
Hideo Yagi ◽  
Ryosuke Fujiwara ◽  
Keigo Sano ◽  
Fujita Mariko ◽  
Takashi Iizuka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Elderly Patients ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
High Response Rate ◽  
High Response ◽  
High Dose ◽  
Weekly Schedule ◽  
High Dose Dexamethasone

Abstract Abstract 1865 Background: The three drugs combination of cyclophosphamide, bortezomib and dexamethasone (CyBorD) has been proven to be a powerful regimen for the treatment of the patients with multiple myeloma (MM). However, twice-weekly schedule of bortezomib and high dose dexamethasone has been shown to cause significant toxicities, including severe peripheral neuropathy (PN). Recently, once-weekly bortezomib induction therapy with CyBorD (modified-CyBorD) has shown less toxicity with high response rate equal to original regimen (Reeder, CB et al. Leukemia 2009). However, more than half of the patients developed bortezomib induced PN (BiPN) in modified-CyBorD. Thus it was still concerned adverse event for the transplant ineligible patients, especially frail elderly patients because it often caused interruption or withdrawal of the treatments, resulting in fewer efficacies. Under these circumstances, we introduced the reduced-dosage of CyBorD regimen (reduced-CyBorD) in the transplant ineligible patients with multiple myeloma for continuation of the treatment. Methods: The protocol consisted of bortezomib given intravenously at a dose of 1.3 mg/m2once a week on days 1, 8, 15, cyclophosphamide orally at a dose of 50 mg daily on days 1–21, and dexamethasone orally or intravenously at a dose of 20 mg daily on days 1,2,8,9,15,16 in 4-week cycles. Total of 20 patients, including 12 newly diagnosed and 8 refractory, were treated with reduced-CyBorD and evaluated its efficacy and safety. Results: The median age was 72 years (range from 62 to 81). 14 patients were more than 70 year-old (70%). A half of the patients were female. According ISS, 3 patients were classified in stage I, 6 were in II, and 11 were in III. The overall response was 86.6 % with 26.7 % CR/nCR (1 CR, 3 nCR, 5 VGPR and 4 PR). Hematological adverse events were neutropenia (35%; G1/2 n=7), lymphocytopenia (35%; G1/2 n=1, G3/4, n=1), thrombocytopenia (10%; G1/2 n=2). Non-hematological adverse events were pneumonia (20%; G2 n=2, G3 n=2), VZV infection (15%; G2 n=3), cerebral infarction (5%; G2 n=1). Importantly, only three patients (15%) developed grade 1 PN, and no patient reduced or discontinued bortezomib due to PN. Conclusions: Reduced-CyBorD with three times once-weekly bortezomib retained high efficacy seen in standard and modified CyBorD (4 times bortezomib administration). Furthermore, it was found that this regimen obviously revealed less toxicity, especially BiPN compared with those previous regimens (See Table). Our results suggested that reduced-CyBorD might be safe and effective approach to the transplant ineligible patients, especially elderly frail patients with MM. Disclosures: No relevant conflicts of interest to declare.

A multicenter phase II neoadjuvant trial of bevacizumab combined with docetaxel plus carboplatin in the treatment of triple-negative breast cancer: Korean Cancer Study Group (KCSG-BR 0905, NCT 01208480).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2542-2542
Author(s):  
Hye Ryun Kim ◽  
Kyung Hae Jung ◽  
Seock-Ah Im ◽  
Young-Hyuck Im ◽  
Seok Yun Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Wound Healing ◽  
Lymph Node ◽  
Adverse Events ◽  
Triple Negative ◽  
Response Rate ◽  
Clinical Response Rate ◽  
Study Group ◽  
Axillary Lymph ◽  
Cancer Study Group

2542 Background: Triple negative breast cancer (TNBC) is dismal disease that is ineligible for endocrine or anti-HER2 therapy. We have conducted a phase II neoadjuvant trial to evaluate efficacy and tolerability of bevacizumab combined with docetaxel plus carboplatin in TNBC. Methods: Women with a histologically confirmed stage II or III TNBC were eligible. Hormone receptors and HER2 negativity were confirmed by immunohistochemistry and/or fluorescence in situ hybridization. Patients received 6 cycles of docetaxel 75 mg/m2, carboplatin AUC 5, and bevacizumab 15 mg/kg on day1 every 21 days. Bevacizumab was omitted in the last cycle to avoid wound complication. The primary endpoint was pathologic complete response (pCR) rate in both breast and axillary lymph node and secondary endpoints were clinical response rate, toxicity profiles, and breast conserving surgery (BCS) rate. Results: Forty-five TNBC patients were recruited from 7 institutes in the Korean Cancer Study Group (KCSG) between October 2010 and August 2011. The median age of the patients was 45 years (30-72 years). The T1, T2, and T3 were 4.4 %, 68.9 %, and 26.7 %, respectively and axillary lymph node was positive in 80% by breast MRI. Among 45 patients, 44 patients completed 6 cycles of therapy followed by surgery and one patient was withdrawn due to patient’s refusal of further therapy after 3rd cycle. The pCR rate was 42.2 % (19/45) and clinical response rate was 95.5 % (43/45) (CR, n= 6; PR, n=37; SD, n=1; not evaluable, n=1) based on RECIST criteria 1.1. BCS was undertaken in 77.7 % (35/45). The grade 3 or 4 adverse events were neutropenia (38), febrile neutropenia (4), vomiting (3), nausea (2), anemia (1), thrombocytopenia (1), stomatitis (1), gastrointestinal bleeding (1), and increased ALT (1). Only one patient experienced delayed wound healing after breast surgery. Conclusions: Bevacizumab in combination with docetaxel and carboplatin as neoadjuvant treatment provided an encouraging pCR rate (42.2 %) and a negligible wound healing problem after surgery. The adverse events were manageable.

Sequential chemotherapy with gemcitabine+carboplatin followed by gemcitabine+carboplatin+docetaxel for advanced upper-tract urothelial cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 428-428
Author(s):  
Takahiro Yoneyama ◽  
Tendo Sato ◽  
Jotaro Mikami ◽  
Yuta Kojima ◽  
Naoki Fujita ◽  
...  
Keyword(s):  
Adverse Events ◽  
Urothelial Cancer ◽  
Response Rate ◽  
High Response Rate ◽  
Sequential Chemotherapy ◽  
Upper Tract ◽  
Limited Effectiveness ◽  
Upper Tract Urothelial Cancer ◽  
Grade 3 ◽  
Observation Period

428 Background: Chemotherapy for advanced upper-tract urothelial cancer (UC) has not yet been established. Gemcitabine+cisplatin may be a promising regimen for advanced upper-tract UC as well as for advanced bladder cancer. However, cases with renal dysfunction are common in advanced upper-tract UC, and cisplatin often unfits for those patients. We retrospectively evaluated the effectiveness and adverse events (AEs) of a sequential chemotherapy with gemcitabine+carboplatin(GCarbo) followed by GCarbo+ docetaxel (GCarboD) for advanced upper-tract UC. Methods: We treated 74 patients (52 men and 22 women) with advanced upper-tract UC from September 2004 to December 2014. Mean age was 69.3 (43–89), and mean Ccr was 50.5 (11.6–99.3) ml/minute. Mean observation period was 24.0 (3–96) months. The patients received 2 courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (70mg/m2) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR. GCarboD treatment was administered in 21 cases, and yielded two (9.5%) PR. The median survival period was 18.3 months with GCarbo/GCarboD regimens. Adverse events (AE) of grade 3 or higher occurred in 48 of those who had undergone the GCarbo therapy (64.9%). In GCarboD regimen, there were 20 (95.2 %) of G3/4 AEs. Conclusions: GCarbo and GCarboD chemotherapy can be administered safely to advanced upper-tract UC cancer, many of whom have renal dysfunctions. GCarbo regimen achieved high response rate (50.0%) in advanced upper-tract UC. However, GCarboD had limited effectiveness for non-responder of GCarbo.

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