Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

OBJECTIVE: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy.
METHODS: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study\'s primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles.
RESULTS: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects.
CONCLUSIONS: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib.

OBJECTIVE: We aimed to assess the relative importance of attributes and the willingness to pay for pharmacological therapies among patients with renal cell carcinoma in China.
METHODS: Patients with renal cell carcinoma completed a D-efficient-designed, discrete-choice experiment online survey that presented a series of ten trade-off questions and one examining scenario. Based on the literature review and consultations with patients with renal cell carcinoma and clinicians, each question included a pair of hypothetical renal cell carcinoma medication profiles characterized by seven attributes including progression-free survival, objective response rate, medication regimen, fatigue, gastrointestinal reaction, hand-foot syndrome, and monthly out-of-pocket costs. Relative importance and willingness to pay were calculated using coefficients estimated by mixed logit regression in the main analysis. Subgroup analyses were conducted considering the heterogeneity of the participants, based on sex, education level, and income level, using conditional logit regression.
RESULTS: The analysis incorporated responses from 182 Chinese respondents. Except for the medication regimen, all attributes were statistically significant. Progression-free survival was the most important attribute, followed by objective response rate, monthly out-of-pocket costs, fatigue, gastrointestinal reaction, and hand-foot syndrome. Patients were willing to pay ￥2010.51 ($298.30), ￥494.93 ($73.43) for 1 unit improvement of progression-free survival, and objective response rate, and￥7558.93 ($1121.50), ￥6927.24 ($1027.78) to avoid experiencing fatigue and gastrointestinal reaction, respectively. Differences in preferences and willingness to pay were found according to patients\' gender, income, and education level.
CONCLUSIONS: In China, patients with renal cell carcinoma preferred medications with better efficacy (objective response rate and progression-free survival) and lower out-of-pocket costs. Heterogeneity can be found in preferences and willingness to pay based on patients\' gender, income, and education levels.

Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.
目的： 探讨安罗替尼治疗晚期肉瘤的有效性和安全性，分析不良反应与疗效间的关系。 方法： 回顾性分析2018年6月至2021年8月在郑州大学附属肿瘤医院接受安罗替尼治疗的45例晚期肉瘤患者的临床资料。根据实体肿瘤疗效评价标准1.1版计算客观缓解率(ORR)和疾病控制率(DCR)，分析无进展生存时间(PFS)与治疗相关不良反应间的关系，生存分析采用Kaplan－Meier法，生存率的比较采用Log rank检验。 结果： 45例患者中，40例患者用药时间超过1.5个月，3个月ORR为7.5%(3/40)，DCR为80.0%(32/40)。全组患者的整体ORR为2.5%(1/40)，DCR为27.5%(11/40)，中位PFS为6.70个月。腺泡状软组织肉瘤患者中位PFS为10.27个月，长于其他亚型的肉瘤患者(P＝0.048)，腺泡状软组织肉瘤、滑膜肉瘤患者的DCR[分别为100.0%(5/5)和100.0%(9/9)]明显优于骨肉瘤患者[(25.0%(1/4)，均P<0.05]。常见的不良反应有促甲状腺素升高(17.8%，8/45)、贫血(15.6%，7/45)、乏力(11.1%，5/45)等，5例患者治疗后出现了3级不良反应。治疗后出现手足综合征患者的PFS(14.10个月)长于未出现手足综合征的患者(6.00个月，P＝0.024)。 结论： 安罗替尼治疗腺泡状软组织肉瘤、滑膜肉瘤的疗效优于其他亚型，治疗后出现手足综合征患者的PFS明显长于未出现手足综合征的患者。.

Background: In patients with metastatic colorectal cancer (mCRC) exhibiting no evidence of disease (NED), this study assessed the efficacy and safety of capecitabine maintenance therapy. Methods: The single-arm, phase II CAMCO trial enrolled mCRC-NED patients after first-line treatment, administering oral capecitabine maintenance for 1 year. Results: A total of 93 patients were enrolled. The primary end point, 3-year disease-free survival, yielded a rate of 51.6% (95% CI: 41.3-62.0%). Secondary end points included a 3-year overall survival rate of 83.9% (95% CI: 76.3-91.5%). Grade 3 adverse events (AE) were observed in seven patients (7.5%). Predominantly grade 1 and 2, the most common AE was hand-foot syndrome. Conclusion: In mCRC-NED patients, capecitabine maintenance demonstrated a manageable 3-year disease-free survival rate of 51.6%, accompanied by manageable AEs. Clinical Trial Registration: NCT01880658 (ClinicalTrials.gov).

OBJECTIVE: To analyze the safety and efficacy of orally administered metronomic capecitabine plus pyrotinib in HER2 positive metastatic breast cancer (MBC) patients, we conducted a prospective phase II study with a single-arm design.
METHODS: HER2 positive patients received oral metronomic capecitabine 500 mg three times a day and pyrotinib 400 mg per day. The primary endpoint was progression-free survival (PFS). Other endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR) and safety.
RESULTS: The study included 50 patients with MBC that was HER2-positive, while 1 patient was excluded due to nonstandard medication. The median PFS and OS was 11.9 months (95%CI 8.8-14.6) and 29.3 months (95%CI 24.4-34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months. The most frequent treatment-related adverse events included hand-foot syndrome, diarrhea, vomiting and nausea. Grade 3 adverse events occurred in 15(30.6%) patients, including hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), and nausea (2.0%). 1 grade 4 adverse event of diarrhea (2.0%) was observed.
CONCLUSIONS: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2 positive metastatic breast cancer patients.

Pegylated liposomal doxorubicin (PLD) has excellent therapeutic efficacy in the treatment of cancers, but can cause serious adverse reactions such as hand-foot syndrome (HFS). Our previous research suggests that both PLD-induced HFS may be associated with injury to tight junctions (TJs) in the skin and that calcium dobesilate (CaD) can alleviate HFS. However, the underlying molecular mechanism is not well understood. Here, we created an in vitro PLD-treated model using Human Microvascular Endothelial Cell line-1 (HMEC-1) and an in vivo HFS rat model to investigate the underlying pathways. Treatment with PLD increased the expression of HYAL-1, CD44, and hyaluronic acid (HA) concentration, while reducing ZO-1 and Claudin-5 expression. Moreover, PLD treatment induced the degradation of higher molecular weight HA to its lower molecular weight counterpart, elevating the permeability of both HEMC-1 cell membranes and rat paw skin capillaries. AD-01 (CD44 inhibitor) inhibited the effect of PLD on the expression of ZO-1 and Claudin-5. Furthermore, CaD treatment suppressed the expression of HYAL-1 and CD44, mitigated HA degradation, and enhanced the expression of ZO-1 and Claudin-5. This resulted in decreased permeability in HEMC-1 cells and rat skin capillaries. In summary, our data suggest that PLD may promote the destruction of TJs via the HA/CD44 pathway, thereby leading to HFS through increased skin permeability and exacerbated doxorubicin extravasation. Moreover, CaD can inhibit this pathway, offering a potential therapeutic avenue to alleviate HFS.

Hand-foot syndrome (HFS) is a widely recognized dose-limiting cutaneous toxicity effect of fluoropyrimidine chemotherapy agents that impairs clinical benefits and treatment outcomes. Even though the cause and pathophysiology of HFS are relatively widely reported, how the toxicity of fluoropyrimidine translates into persistent inflammation has not been studied. Additionally, prevention and treatment strategies for HFS based on its mechanistic occurrence and development are scarce. In our study, we demonstrated that cGAS-STING signaling pathway-mediated cellular senescence played a critical role in the inflammatory reaction and provided a therapeutic solution for HFS. Mechanistically, DNA damage, as the primary cytotoxic cause, in keratinocytes induces cell cycle arrest, activates the cGAS-STING signaling pathway, and subsequently mediates cellular senescence, ultimately fueling a robust secondary inflammatory response that results in HFS. More importantly, the thymidine prodrug thymidine diacetate was proven to be effective in preventing HFS by compensating for thymidylate deficiency to facilitate the replication and repair of DNA and thus causing the escape from cellular senescence. These data highlight the importance of DNA damage-mediated cellular senescence in the etiology of HFS and provide a potential therapeutic anchor point for fluoropyrimidine-induced HFS.

BACKGROUND: Multikinase inhibitors (MKIs) treatment has been proven as a powerful strategy in cancer therapy. However, it is greatly hampered by its common adverse effect known as hand-foot skin reaction (HFSR), especially in patients with moderate-to-severe HFSR.
OBJECTIVE: To investigate the clinical characteristics, histopathological features, treatment response, and bio-indicators of HFSR.
METHODS: We retrospectively reviewed the medical records of 102 patients with moderate-to-severe HFSR resulting from MKIs therapy.
RESULTS: The median time to development of moderate-to-severe HFSR was 18 days, which would be significantly affected by the type of MKIs and the history of HFSR. Notably, we found that HFSR was classified into three consecutive stages: erythematous lesion, yellow hyperkeratotic lesion with surrounding erythema, and hyperkeratotic lesion. Inflammation was observed in the first two stages of HFSR, but disappeared in the third stage; in contrast, the hyperkeratosis gradually became thicker from stage one to stage three. Moreover, topical medications were demonstrated as an effective therapy for HFSR, among which, the topical steroids and urea ointment treatment response rate was 37.14%, the Shouzu Ning Decoction (SND) treatment response rate was 65%, and the SND in combination with urea ointment treatment response rate was 75%, meanwhile, systemic therapies did not improve the therapeutic efficacy of topical medications alone. In addition, the serum levels of HMGB1 were found to be a potential indicator for tracking the healing process as well as predicting the prognosis of HFSR.
CONCLUSIONS: This study revealed the potential factors affecting the development of HFSR, evaluated the therapeutic response towards different strategies for treating HFSR, and identified a potential prognostic indicator of HFSR.

OBJECTIVE: To systematically evaluate the prevalence of hand-foot syndrome (HFS) in patients with colorectal cancer undergoing chemotherapy.
METHODS: The PubMed, Embase, and Cochrane Library databases were searched, from their inception to September 20, 2022, to identify studies on the prevalence of HFS in patients with colorectal cancer receiving chemotherapy. Comprehensive retrieval of literature was performed using the literature tracing method. We calculated the prevalence of HFS in patients with colorectal cancer undergoing chemotherapy based on meta-analyses. Subgroup analysis and meta-regression analyses were performed to determine the sources of heterogeneity.
RESULTS: A total of 20 studies were included, involving 4773 cases. Meta-analysis of the random effects model showed that the total prevalence of HFS in patients with colorectal cancer undergoing chemotherapy was 49.1% (95% confidence interval [CI]: 0.332, 0.651). Subgroup analysis demonstrated that the most frequent grades of HFS were grades 1 and 2, accounting for 40.1% (95% CI: 0.285, 0.523) of cases; this rate was markedly higher than that of grades 3 and 4 (5.8%; 95% CI: 0.020, 0.112). The meta-regression results illustrated that the type of research, country of the study population, type of drug, and year of publication were not sources of heterogeneity in this setting (P > 0.05).
CONCLUSIONS: The present findings showed that the prevalence of HFS in patients with colorectal cancer receiving chemotherapy was high. Healthcare professionals should provide knowledge to such patients regarding the prevention and management of HFS.