Marie S Dreyer,Mary Mulcahy,Masha Kocherginsky,Yolande Chen,Howard S Hochster,Pashtoon M Kasi,Sheetal Kircher,Emil Lou,Yangruijue Ma,Nataliya V Uboha,Al B Benson
BACKGROUNDDoublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Previously used anthracycline-based triplet regimens are no longer used routinely due to toxicity and lack of superior efficacy. We hypothesized that the addition of nab-paclitaxel to FOLFOX (FOLFOX-A) would induce higher efficacy and better tolerability.PATIENTS AND METHODSEligible patients with chemotherapy-naïve advanced unresectable HER2-negative gastric or GEJ adenocarcinoma were enrolled in this phase II single-arm trial of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46-48 hours) + nab-paclitaxel (150 mg/m2) every 14 days of a 28-day cycle. Evaluable disease according to RECIST v1.1 for solid tumors was required. The primary endpoint was the objective response rate. Simon's optimal 2-stage design was used to test 5% versus 20% response rate with 90% power and 10% one-sided type I error rate.RESULTSThe study enrolled 39 patients. Median age was 63 (range 20-80) years, 30 (77%) were male, 34 (94%) were White, and 21 (57%) had gastric tumors. The median number of cycles completed was 4.5 (range: 0-36), and 25 patients required dose reductions or discontinuation of at least one component due to toxicity. Of the 38 patients evaluable for response, 15 (42.9%) had complete/partial response (CR/PR) as the best response, and 13 (37.1%) had stable disease. progression-free survival (PFS) and OS data were available for 38 patients, with a median follow-up duration of 27 months (range: 18.2-51.9 months for censored patients). Median PFS was 6.6 months (95% CI: 5.6-12.9), with 31.0% (95% CI: 18.4%-52.4%) 12-month PFS rate. The median OS was 10.5 months (95% CI: 8.8-20.7), 12-month OS rate was 44.7% (95% CI: 31.4%-63.7%). Treatment-related grade 3-4 toxicities included peripheral sensory neuropathy and anemia (18.4% each), neutropenia (15.8%), and diarrhea and lymphopenia (7.9% each).CONCLUSIONSFOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.
{"title":"A phase II study of FOLFOX combined with nab-paclitaxel in the treatment of metastatic or advanced unresectable gastric, gastroesophageal junction adenocarcinoma: a Big Ten Cancer Research Consortium trial.","authors":"Marie S Dreyer,Mary Mulcahy,Masha Kocherginsky,Yolande Chen,Howard S Hochster,Pashtoon M Kasi,Sheetal Kircher,Emil Lou,Yangruijue Ma,Nataliya V Uboha,Al B Benson","doi":"10.1093/oncolo/oyae236","DOIUrl":"https://doi.org/10.1093/oncolo/oyae236","url":null,"abstract":"BACKGROUNDDoublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Previously used anthracycline-based triplet regimens are no longer used routinely due to toxicity and lack of superior efficacy. We hypothesized that the addition of nab-paclitaxel to FOLFOX (FOLFOX-A) would induce higher efficacy and better tolerability.PATIENTS AND METHODSEligible patients with chemotherapy-naïve advanced unresectable HER2-negative gastric or GEJ adenocarcinoma were enrolled in this phase II single-arm trial of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46-48 hours) + nab-paclitaxel (150 mg/m2) every 14 days of a 28-day cycle. Evaluable disease according to RECIST v1.1 for solid tumors was required. The primary endpoint was the objective response rate. Simon's optimal 2-stage design was used to test 5% versus 20% response rate with 90% power and 10% one-sided type I error rate.RESULTSThe study enrolled 39 patients. Median age was 63 (range 20-80) years, 30 (77%) were male, 34 (94%) were White, and 21 (57%) had gastric tumors. The median number of cycles completed was 4.5 (range: 0-36), and 25 patients required dose reductions or discontinuation of at least one component due to toxicity. Of the 38 patients evaluable for response, 15 (42.9%) had complete/partial response (CR/PR) as the best response, and 13 (37.1%) had stable disease. progression-free survival (PFS) and OS data were available for 38 patients, with a median follow-up duration of 27 months (range: 18.2-51.9 months for censored patients). Median PFS was 6.6 months (95% CI: 5.6-12.9), with 31.0% (95% CI: 18.4%-52.4%) 12-month PFS rate. The median OS was 10.5 months (95% CI: 8.8-20.7), 12-month OS rate was 44.7% (95% CI: 31.4%-63.7%). Treatment-related grade 3-4 toxicities included peripheral sensory neuropathy and anemia (18.4% each), neutropenia (15.8%), and diarrhea and lymphopenia (7.9% each).CONCLUSIONSFOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.","PeriodicalId":520103,"journal":{"name":"The Oncologist","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Understanding the experiences of community oncology practices in recruiting informal (unpaid/family) caregivers into research studies can inform strategies to improve caregiver enrollment. We used data from the 2022 National Cancer Institute Community Oncology Research Program (NCORP) Landscape Assessment to describe the experience of recruiting informal caregivers for research studies in community oncology practices. Among 258 practice groups, only one-third (30%, 78/258) reported prior experience recruiting informal caregivers for research studies. In multivariable logistic analyses, having a greater number of oncology providers (increase per 10 providers, adjusted odds ratio [AOR] 1.16, 95% CI 1.03-1.31) and having advanced practice providers (APPs) involved in research (AOR 2.17, 95% CI 1.05-4.48) were significantly associated with prior experience recruiting caregivers. In conclusion, many community oncology practices lack caregiver recruitment experience and may benefit from education, integration of APPs/caregiver stakeholders in research infrastructure, and/or other strategies to improve caregiver recruitment.
了解社区肿瘤治疗机构在招募非正式（无偿/家庭）照护者参与研究方面的经验可以为改善照护者招募策略提供参考。我们利用 2022 年美国国家癌症研究所社区肿瘤学研究计划（NCORP）景观评估的数据，描述了社区肿瘤学实践中招募非正式护理人员参与研究的经验。在 258 个实践小组中，只有三分之一（30%，78/258）的小组报告了招募非正式护理人员参与研究的经验。在多变量逻辑分析中，拥有更多肿瘤科医疗人员（每 10 名医疗人员增加一名，调整赔率比 [AOR] 1.16，95% CI 1.03-1.31）和拥有参与研究的高级医疗人员 (APP)（AOR 2.17，95% CI 1.05-4.48）与之前招募护理人员的经验显著相关。总之，许多社区肿瘤学实践缺乏招募护理人员的经验，可能会受益于教育、将 APPs/护理人员利益相关者纳入研究基础设施和/或其他改善护理人员招募的策略。
{"title":"Recruitment of informal caregivers into community oncology research studies: results from the 2022 Landscape Assessment.","authors":"Ying Wang,Chandylen L Nightingale,Christa Braun-Inglis,Katherine Sterba,Kathryn E Weaver,Eden Wood,Sindhuja Kadambi,Umang Gada,Alexander Montes,Allison Magnuson,Sule Yilmaz,Eva Culakova,Sarah Strause,Charles Kamen,Marie Flannery,Karen Mustian,Gary Morrow,Supriya Mohile,Kah Poh Loh,","doi":"10.1093/oncolo/oyae247","DOIUrl":"https://doi.org/10.1093/oncolo/oyae247","url":null,"abstract":"Understanding the experiences of community oncology practices in recruiting informal (unpaid/family) caregivers into research studies can inform strategies to improve caregiver enrollment. We used data from the 2022 National Cancer Institute Community Oncology Research Program (NCORP) Landscape Assessment to describe the experience of recruiting informal caregivers for research studies in community oncology practices. Among 258 practice groups, only one-third (30%, 78/258) reported prior experience recruiting informal caregivers for research studies. In multivariable logistic analyses, having a greater number of oncology providers (increase per 10 providers, adjusted odds ratio [AOR] 1.16, 95% CI 1.03-1.31) and having advanced practice providers (APPs) involved in research (AOR 2.17, 95% CI 1.05-4.48) were significantly associated with prior experience recruiting caregivers. In conclusion, many community oncology practices lack caregiver recruitment experience and may benefit from education, integration of APPs/caregiver stakeholders in research infrastructure, and/or other strategies to improve caregiver recruitment.","PeriodicalId":520103,"journal":{"name":"The Oncologist","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
For women diagnosed with cancer, side effects affecting their sexuality are extremely common and can be distressing and life-changing; however, most women are left in the dark without any guidance from their oncology teams regarding possible side effects and treatment options. American Society of Clinical Oncology clinical guidelines provide guidance on the recommended assessments related to the domains of sexual function and their respective interventions. Despite the existence of these guidelines, the reality is that only a few women with cancer are asked about sexual concerns that result from cancer treatments. Common barriers to sexuality discussion reported by oncology providers include a lack of qualification and knowledge, not having a place to refer patients, and not knowing how to start the conversation. Social media remains a widely untapped resource regarding sexuality and cancer interventions, as people are increasingly turning to social media for health information and advice. This may be especially relevant for sexuality, as oncologists may not feel comfortable or well-trained to discuss the topic, and patients may be reluctant to bring up sexual concerns during their visits. Social media can play a critical role in studying sexual health and in sexuality interventions, particularly in adolescent and young adult patients with cancer. Here, we discuss the lack of inclusion regarding sexuality in oncology, the rates of sexual dysfunction in patients with cancer, treatment options for common sexual concerns, how to utilize the reach of various social media channels, and provide patient and provider resources.
{"title":"From diagnosis to survivorship addressing the sexuality of women during cancer.","authors":"Rebekah Kaufman,Laila Agrawal,Eleonora Teplinsky,Lauren Kiel,Oyepeju Abioye,Narjust Florez","doi":"10.1093/oncolo/oyae242","DOIUrl":"https://doi.org/10.1093/oncolo/oyae242","url":null,"abstract":"For women diagnosed with cancer, side effects affecting their sexuality are extremely common and can be distressing and life-changing; however, most women are left in the dark without any guidance from their oncology teams regarding possible side effects and treatment options. American Society of Clinical Oncology clinical guidelines provide guidance on the recommended assessments related to the domains of sexual function and their respective interventions. Despite the existence of these guidelines, the reality is that only a few women with cancer are asked about sexual concerns that result from cancer treatments. Common barriers to sexuality discussion reported by oncology providers include a lack of qualification and knowledge, not having a place to refer patients, and not knowing how to start the conversation. Social media remains a widely untapped resource regarding sexuality and cancer interventions, as people are increasingly turning to social media for health information and advice. This may be especially relevant for sexuality, as oncologists may not feel comfortable or well-trained to discuss the topic, and patients may be reluctant to bring up sexual concerns during their visits. Social media can play a critical role in studying sexual health and in sexuality interventions, particularly in adolescent and young adult patients with cancer. Here, we discuss the lack of inclusion regarding sexuality in oncology, the rates of sexual dysfunction in patients with cancer, treatment options for common sexual concerns, how to utilize the reach of various social media channels, and provide patient and provider resources.","PeriodicalId":520103,"journal":{"name":"The Oncologist","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDFosnetupitant, a neurokinin-1 receptor antagonist, is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Previous phase III trials demonstrated the non-inferiority of its 30-minute infusion to fosaprepitant in efficacy and a favorable safety profile.METHODSThis was a single-arm, phase II study to investigate the safety of a 15-minute infusion of fosnetupitant in patients with gastrointestinal and breast cancer. Patients who had received their dose of fosnetupitant in a 30-minute infusion without developing an allergic reaction were eligible and received their next fosnetupitant dose for 15 minutes. The primary endpoint was the incidence of an allergic reaction during the first 15-minutes infusion, and the secondary endpoints were the incidence of injection site reaction (ISR), the incidence of a grade ≥ 3 treatment-related adverse event (TRAE) with fosnetupitant, and complete response (CR) rate.RESULTSThe study period was from February 17, 2023 to June 20, 2023. In an exploratory analysis, medical records from the end of the study period to December 31, 2023 were retrospectively evaluated to assess the time-saving effect and safety of the short-term infusion of fosnetupitant. Fifty-six patients with gastrointestinal and 14 patients with breast cancer were enrolled, one of whom with breast cancer did not receive study treatment at her own request. No allergic reactions occurred during the 15-minutes infusion. Furthermore, there were no allergic reactions across all 280 short-term injections (Table 1). Additionally, no ISR or grade 3 or higher TRAE were reported. The CR rate was 87.0%.CONCLUSIONShort-term infusion of fosnetupitant, administered over 15 minutes, was demonstrated to be safe and effective for patients receiving HEC or MEC (Japan Registry of Clinical Trials Trial ID: jRCT1041220144).
{"title":"Safety of a short-term infusion of fosnetupitant in patients with gastrointestinal and breast cancer: a prospective study.","authors":"Akinobu Nakata,Naoya Hashimoto,Yukiya Narita,Munehiro Wakabayashi,Hiroyuki Kodama,Takatsugu Ogata,Kazunori Honda,Toshiki Masuishi,Hiroya Taniguchi,Shigenori Kadowaki,Masashi Ando,Yuka Endo,Haruru Kotani,Ayumi Kataoka,Masaya Hattori,Akiyo Yoshimura,Masataka Sawaki,Kazuki Nozawa,Isao Oze,Hiroji Iwata,Kei Muro","doi":"10.1093/oncolo/oyae223","DOIUrl":"https://doi.org/10.1093/oncolo/oyae223","url":null,"abstract":"BACKGROUNDFosnetupitant, a neurokinin-1 receptor antagonist, is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Previous phase III trials demonstrated the non-inferiority of its 30-minute infusion to fosaprepitant in efficacy and a favorable safety profile.METHODSThis was a single-arm, phase II study to investigate the safety of a 15-minute infusion of fosnetupitant in patients with gastrointestinal and breast cancer. Patients who had received their dose of fosnetupitant in a 30-minute infusion without developing an allergic reaction were eligible and received their next fosnetupitant dose for 15 minutes. The primary endpoint was the incidence of an allergic reaction during the first 15-minutes infusion, and the secondary endpoints were the incidence of injection site reaction (ISR), the incidence of a grade ≥ 3 treatment-related adverse event (TRAE) with fosnetupitant, and complete response (CR) rate.RESULTSThe study period was from February 17, 2023 to June 20, 2023. In an exploratory analysis, medical records from the end of the study period to December 31, 2023 were retrospectively evaluated to assess the time-saving effect and safety of the short-term infusion of fosnetupitant. Fifty-six patients with gastrointestinal and 14 patients with breast cancer were enrolled, one of whom with breast cancer did not receive study treatment at her own request. No allergic reactions occurred during the 15-minutes infusion. Furthermore, there were no allergic reactions across all 280 short-term injections (Table 1). Additionally, no ISR or grade 3 or higher TRAE were reported. The CR rate was 87.0%.CONCLUSIONShort-term infusion of fosnetupitant, administered over 15 minutes, was demonstrated to be safe and effective for patients receiving HEC or MEC (Japan Registry of Clinical Trials Trial ID: jRCT1041220144).","PeriodicalId":520103,"journal":{"name":"The Oncologist","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 and LRP1B, which notably outperformed mere mutation status in prognostic predictions. These gene signatures remained prognostically valuable even when accounting for clinical factors, including cytogenetic abnormalities, the International Staging System (ISS), and its revised version (R-ISS). The LRP1B signature effectively distinguished high-risk patients within low/intermediate-risk categories and correlated with significant changes in the tumor immune microenvironment. Additionally, the LRP1B signature showed a strong association with proteasome inhibitor pathways, notably predicting patient responses to bortezomib and the progression from monoclonal gammopathy of unknown significance to MM. Through a rigorous analysis, this study underscores the potential of specific gene signatures in revolutionizing the prognostic landscape of MM, providing novel clinical insights that could influence future translational oncology research.
在多发性骨髓瘤（MM）中，虽然驱动基因的频繁突变对疾病进展至关重要，但传统上它们对患者预后的影响有限。本研究旨在通过分析关键癌症驱动基因的通路失调，从而确定可操作的基因特征，从而提高对多发性骨髓瘤预后的认识。我们对 MM 中 10 个频繁突变的癌症驱动基因的突变和通路失调进行了详细的量化，以描述其突变对整个转录组的全面影响。随后，我们进行了系统的生存分析，以确定具有更高预后价值的重要基因特征。我们的系统分析突出了两个重要的特征，即 TP53 和 LRP1B，它们在预后预测方面的效果明显优于单纯的突变状态。即使考虑细胞遗传学异常、国际分期系统（ISS）及其修订版（R-ISS）等临床因素，这些基因特征仍具有预后价值。LRP1B 基因特征能有效区分低危/中危类别中的高危患者，并与肿瘤免疫微环境的显著变化相关。此外，LRP1B特征还与蛋白酶体抑制剂通路密切相关，尤其能预测患者对硼替佐米的反应，以及从意义不明的单克隆淋巴瘤发展为MM的过程。通过严格的分析，这项研究强调了特定基因特征在改变 MM 预后方面的潜力，提供了新的临床见解，可能会影响未来的肿瘤转化研究。
{"title":"Characterization of driver mutations identifies gene signatures predictive of prognosis and treatment sensitivity in multiple myeloma.","authors":"Jian-Rong Li,Abinand Krishna Parthasarathy,Aravind Singaram Kannappan,Shahram Arsang-Jang,Jing Dong,Chao Cheng","doi":"10.1093/oncolo/oyae244","DOIUrl":"https://doi.org/10.1093/oncolo/oyae244","url":null,"abstract":"In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 and LRP1B, which notably outperformed mere mutation status in prognostic predictions. These gene signatures remained prognostically valuable even when accounting for clinical factors, including cytogenetic abnormalities, the International Staging System (ISS), and its revised version (R-ISS). The LRP1B signature effectively distinguished high-risk patients within low/intermediate-risk categories and correlated with significant changes in the tumor immune microenvironment. Additionally, the LRP1B signature showed a strong association with proteasome inhibitor pathways, notably predicting patient responses to bortezomib and the progression from monoclonal gammopathy of unknown significance to MM. Through a rigorous analysis, this study underscores the potential of specific gene signatures in revolutionizing the prognostic landscape of MM, providing novel clinical insights that could influence future translational oncology research.","PeriodicalId":520103,"journal":{"name":"The Oncologist","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lessons learned: Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild-type unresectable colorectal cancer. It is especially effective for left-sided tumors; therefore, panitumumab as first-line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin-based or irinotecan-based combination regimens.
Background: First-line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy-naïve frail or elderly patients with unresectable RAS wild-type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first-line treatment.
Methods: We conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities.
Results: Thirty-six patients (median age: 81 [range, 67-88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty-three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty-eight patients (77.8%) had left-sided CRC, whereas eight (22.2%) had right-sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4-67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5-87.7). The RR of patients with left- and right-sided tumors was 65.4% (95% CI, 44.3-82.8) and 0.0% (95% CI, 0.0-36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%).
Conclusion: Panitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.
{"title":"Phase II Study of Panitumumab Monotherapy in Chemotherapy-Naïve Frail or Elderly Patients with Unresectable RAS Wild-Type Colorectal Cancer: OGSG 1602.","authors":"Tetsuji Terazawa, Takeshi Kato, Masahiro Goto, Katsuya Ohta, Shingo Noura, Hironaga Satake, Yoshinori Kagawa, Hisato Kawakami, Hiroko Hasegawa, Kazuhiro Yanagihara, Tatsushi Shingai, Ken Nakata, Masahito Kotaka, Masayuki Hiraki, Ken Konishi, Shiro Nakae, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh","doi":"10.1002/ONCO.13523","DOIUrl":"https://doi.org/10.1002/ONCO.13523","url":null,"abstract":"<p><strong>Lessons learned: </strong>Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild-type unresectable colorectal cancer. It is especially effective for left-sided tumors; therefore, panitumumab as first-line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin-based or irinotecan-based combination regimens.</p><p><strong>Background: </strong>First-line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy-naïve frail or elderly patients with unresectable RAS wild-type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first-line treatment.</p><p><strong>Methods: </strong>We conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities.</p><p><strong>Results: </strong>Thirty-six patients (median age: 81 [range, 67-88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty-three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty-eight patients (77.8%) had left-sided CRC, whereas eight (22.2%) had right-sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4-67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5-87.7). The RR of patients with left- and right-sided tumors was 65.4% (95% CI, 44.3-82.8) and 0.0% (95% CI, 0.0-36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%).</p><p><strong>Conclusion: </strong>Panitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.</p>","PeriodicalId":520103,"journal":{"name":"The Oncologist","volume":" ","pages":"17-e47"},"PeriodicalIF":5.8,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ONCO.13523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38371454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-12-01DOI: 10.1634/theoncologist.2002-0029
Laura Biganzoli,Miguel Martin,Chris Twelves
Abstract Learning Objectives After completing this course, the reader will be able to: Appreciate the emerging role of capecitabine monotherapy in the treatment of advanced breast cancer. Explain the current status of capecitabine monotherapy as first or second line therapy in patients with advanced breast cancer. Describe the rationale and current status of capecitabine combination treatment of breast cancer. Balance the safety profile of capecitabine with available alternative treatment options for the treatment of advanced breast cancer. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Oral capecitabine is a useful chemotherapy for metastatic breast cancer, both as monotherapy and in combination with other cytotoxic drugs. The proven activity of capecitabine has provided the rationale to explore its use earlier in the course of the disease and in combination with other agents, particularly those known to further upregulate thymidine phosphorylase (TP) concentrations in tumor tissue. The efficacy and safety of capecitabine monotherapy compares favorably with cyclophosphamide/methotrexate/5-fluorouracil in chemotherapy-naïve patients and with paclitaxel in anthracycline-pretreated patients. Therefore, for patients whose disease has progressed during or following anthracycline treatment, but for whom capecitabine/docetaxel combination therapy or taxane monotherapy is not appropriate, capecitabine monotherapy is an attractive alternative to established i.v. treatments. In combination, capecitabine plus paclitaxel, which further upregulates TP in tumor tissue, has demonstrated high activity in two phase II studies in advanced/metastatic breast cancer. Similarly, combination with vinorelbine showed promising activity in pretreated metastatic breast cancer patients, and triple combinations with an anthracycline and a taxane or cyclophosphamide have proven to be highly active. In the future, capecitabine may be combined with novel biologic agents, such as trastuzumab and bevacizumab; the former combination has already shown encouraging results in a pilot trial. Confirmatory studies for many of these combinations and phase III trials versus standard therapy are now warranted.
摘要 学习目标 完成本课程后，读者将能够 了解卡培他滨单药在晚期乳腺癌治疗中的新作用。解释卡培他滨单药作为晚期乳腺癌患者一线或二线疗法的现状。描述卡培他滨联合治疗乳腺癌的原理和现状。平衡卡培他滨与现有晚期乳腺癌替代疗法的安全性。 在 CME.TheOncologist.com 上在线访问并参加 CME 测试，即可获得 1 小时 AMA PRA 1 类学分。口服卡培他滨是治疗转移性乳腺癌的有效化疗药物，既可作为单一疗法，也可与其他细胞毒性药物联合使用。卡培他滨的活性已得到证实，因此有理由探索在疾病的早期阶段将其与其他药物联合使用，特别是那些已知会进一步上调肿瘤组织中胸腺嘧啶磷酸化酶（TP）浓度的药物。 卡培他滨单药治疗的疗效和安全性与环磷酰胺/甲氨蝶呤/5-氟尿嘧啶治疗化疗无效患者的疗效和安全性以及紫杉醇治疗蒽环类药物治疗患者的疗效和安全性相比都更胜一筹。因此，对于在蒽环类药物治疗期间或治疗后病情出现进展，但不适合接受卡培他滨/多西他赛联合疗法或类固醇单药疗法的患者，卡培他滨单药疗法是既有静脉注射疗法的一种有吸引力的替代疗法。 在晚期/转移性乳腺癌的两项 II 期研究中，卡培他滨与紫杉醇的联合治疗显示了很高的活性，紫杉醇可进一步上调肿瘤组织中的 TP。同样，卡培他滨与长春瑞滨的联合用药在预处理的转移性乳腺癌患者中也显示出良好的活性，而蒽环类药物与类固醇或环磷酰胺的三联用药也被证明具有很高的活性。未来，卡培他滨可能会与新型生物制剂（如曲妥珠单抗和贝伐单抗）联合使用；前者已经在一项试点试验中取得了令人鼓舞的结果。现在需要对其中许多组合进行确认性研究，并进行与标准疗法对比的 III 期试验。
{"title":"Moving Forward with Capecitabine: a Glimpse of the Future","authors":"Laura Biganzoli,Miguel Martin,Chris Twelves","doi":"10.1634/theoncologist.2002-0029","DOIUrl":"https://doi.org/10.1634/theoncologist.2002-0029","url":null,"abstract":"Abstract Learning Objectives After completing this course, the reader will be able to: Appreciate the emerging role of capecitabine monotherapy in the treatment of advanced breast cancer. Explain the current status of capecitabine monotherapy as first or second line therapy in patients with advanced breast cancer. Describe the rationale and current status of capecitabine combination treatment of breast cancer. Balance the safety profile of capecitabine with available alternative treatment options for the treatment of advanced breast cancer. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Oral capecitabine is a useful chemotherapy for metastatic breast cancer, both as monotherapy and in combination with other cytotoxic drugs. The proven activity of capecitabine has provided the rationale to explore its use earlier in the course of the disease and in combination with other agents, particularly those known to further upregulate thymidine phosphorylase (TP) concentrations in tumor tissue. The efficacy and safety of capecitabine monotherapy compares favorably with cyclophosphamide/methotrexate/5-fluorouracil in chemotherapy-naïve patients and with paclitaxel in anthracycline-pretreated patients. Therefore, for patients whose disease has progressed during or following anthracycline treatment, but for whom capecitabine/docetaxel combination therapy or taxane monotherapy is not appropriate, capecitabine monotherapy is an attractive alternative to established i.v. treatments. In combination, capecitabine plus paclitaxel, which further upregulates TP in tumor tissue, has demonstrated high activity in two phase II studies in advanced/metastatic breast cancer. Similarly, combination with vinorelbine showed promising activity in pretreated metastatic breast cancer patients, and triple combinations with an anthracycline and a taxane or cyclophosphamide have proven to be highly active. In the future, capecitabine may be combined with novel biologic agents, such as trastuzumab and bevacizumab; the former combination has already shown encouraging results in a pilot trial. Confirmatory studies for many of these combinations and phase III trials versus standard therapy are now warranted.","PeriodicalId":520103,"journal":{"name":"The Oncologist","volume":"17 1","pages":"29-35"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：