Clinical efficacy of pemetrexed disodium in maintenance treatment of advanced lung adenocarcinoma / 中国基层医药

Objective:To investigate the clinical efficacy and adverse reactions of pemetrexed disodium in the maintenance treatment of advanced lung adenocarcinoma after chemotherapy with pemetrexed disodium and platinum.Methods:The clinical data of 35 patients with stage Ⅳ lung adenocarcinoma who received chemotherapy with pemetrexed disodium and platinum and were well treated in Beijing Huairou Hospital from January 2013 to August 2020 were retrospectively analyzed. Maintenance therapy with pemetrexed disodium was initiated after the completion of combination chemotherapy until disease progression. The clinical characteristics, therapeutic effects, adverse reactions, progression-free survival, and overall survival of the 35 patients were evaluated.Results:Among the 35 patients, no patients had complete remission, 11 patients had partial remission, 22 patients had stable disease, and 2 patients had progressive disease. The objective remission rate was 31.4%, disease control rate was 94.3%, median progression-free survival was 9.53 months, median overall survival was 18.21 months, 1-year survival rate was 68.6%, 2-year survival rate was 31.4%, and 3-year survival rate was 11.4%. Gender, age, smoking, and the baseline characteristics of patients undergoing first-line pemetrexed disodium or second-line pemetrexed disodium treatment had no effects on progression-free survival (all P > 0.05). Positive gene mutation and receiving four or more chemotherapy cycles had a protective effect on progression-free survival (both P < 0.05). Chemotherapy-related adverse reactions mainly included myelosuppression, nausea, elevated transaminase, and nephrotoxicity, all of which were mild and were relieved after symptomatic treatment. Conclusion:Pemetrexed disodium is effective and safe in the maintenance treatment of advanced lung adenocarcinoma. The results of this study are scientific.

Real-world clinical data analysis of PARPi as first-line maintenance therapy in newly diagnosed epithelial ovarian cancer patients / 中华妇产科杂志

Objective:The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored.Methods:(1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed.Results:(1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95% CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95% CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions:Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

Capecitabine maintenance in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study / 中国肿瘤临床

Objective: The efficacy of sequential capecitabine maintenance chemotherapy after radical chemoradiotherapy for stage N2- 3 nasopharyngeal carcinoma in non- endemic areas of northwest China was retrospectively analyzed to clarify the value of capecitabine maintenance chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma. Methods: From Jannary 2014 to December 2016, patients with stage N2-3 nasopharyngeal carcinoma underwent 2 or 3 cycles of induction chemotherapy combined with concurrent chemoradiotherapy. The study group continued to receive capecitabine for 4 cycles of chemotherapy after radical chemoradiotherapy, whereas the control group was only observed. The survival differences between the two groups were compared, and the toxicity and compliance of the two regimens were evaluated. Result: A total of 179 patients were included in this study, among whom 84 were included in the maintain chemotherapy group and 95 in the control group. The median follow-up time was 44.4 (5.97-70.26) months. The 3-year distant metastasis-free survival rates and 3-year disease-free survival rates were 79.3% and 68.1% (chi-square=3.898, P=0.048) and 75.6% and 64.2% (chi-square=5.428, P=0.020) for the maintain chemotherapy and control groups, respectively. The differences were statistically significant. There was no difference between the two groups in acute and late toxicity (P> 0.05). The toxicity of capecitabine-specific drugs was below grade 2. Conclusions: For N2-3 stage nasopharyngeal carcinoma in non-endemic areas in northwest China, the 3- year distant metastasis- free survival and disease- free survival rates following sequential capecitabine maintenance therapy after radical radiotherapy and chemotherapy are improved. Treatment was well-tolerated, and compliance was good, with no obvious adverse reactions.

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group / 부인종양

Severe recurrent nocturnal hypoglycemia during chemotherapy with 6-mercaptopurine in a child with acute lymphoblastic leukemia

Various endocrine dysfunctions occur during chemotherapy, including hypoglycemia. However, reports of hypoglycemia associated with 6-mercaptopurine (6-MP) are rare. Herein, we report an 8-year-old boy with severe symptomatic hypoglycemia likely due to 6-MP during chemotherapy. He had been diagnosed with acute lymphoblastic leukemia 3 years previously and was in the maintenance chemotherapy period. Treatment included oral dexamethasone, methotrexate, and 6-MP, of which only 6-MP was administered daily. Hypoglycemic symptoms appeared mainly at dawn, and his serum glucose dropped to a minimum of 37 mg/dL. Laboratory findings showed nothing specific other than increased serum cortisol, free fatty acids, ketone, alanine aminotransferase, and aspartate aminotransferase. Under the hypothesis of hypoglycemia due to chemotherapy drugs, we changed the time of 6-MP from evening to morning and recommended him to ingest carbohydrate-rich foods before bedtime. Hypoglycemia improved dramatically, and there was no further episode during the remaining maintenance chemotherapy period. To the best of our knowledge, this is the first report of this type of hypoglycemia occurring in an Asian child including Korean.

Clinical significance of centralized surveillance of hydatidiform mole / 中华妇产科杂志

Objective To explore the clinical significance of centralized surveillance of hydatidiform mole.Methods From Feb.2013 to Feb.2017 all patients with hydatidiform mole,who underwent suction curettage and were confirmed by histopathology in Dalian Maternal and Child Health Care Hospital,were registered centrally for serum hCG monitoring and treatment if necessary.Prophylactic chemotherapy was not administered regardless of risk factors for malignant transformation of hydatidiform mole.The risk factors included age of over 40 years,excessive uterine enlargement for presumed gestational age,a serum hCG level greater than 5 00 000 U/L,large theca lutein ovarian cysts (＞6 cm),and a history of previous hydatidiform mole.The centralized surveillance of hydatidiform mole was based on the central pathology review,team cooperation and service improvement.Their treatments and outcomes were analyzed retrospectively.Results A total of 407 women of hydatidiform mole were registered with histopathology confirmation,including 70 high-risk hydatidiform moles.The follow-up rate was 97.5％ (397/407).The incidence of post-mole neoplasia was 8.1％ (32/397),which was diagnosed in 22.9％ (16/70) of high-risk and in 4.9％ (16/327) of low-risk hydatidiform moles,showed statistically significant difference between high-risk and low-risk groups (x2=25.108,P＜0.01).Thirty-two patients with post-mole neoplasia were all at low risk of International Federation of Gynecology and Obstetrics (FIGO) score (range,0-6) and received complete remission with chemotherapy alone in 31 of them except one treated by hysterectomy.The primary cure rate of single-agent chemotherapy was 60.0％ (18/30).Patients with low-risk or high-risk post-mole neoplasia were both 16.There were no significant differences between the two groups in interval that was end of antecedent pregnancy to start of treatment,the serum level of hCG before treatment,clinical stage or risk factor score (all P＞0.05).Conclusions The risk of malignant transformation is increased in high-risk hydatidiform mole,however,the high risk factor itself does not affect the prognosis in patients with timely diagnosis and treatment of post-mole neoplasia.Therefore,prophylactic chemotherapy is not recommended to high-risk hydatidiform mole patients.Centralized surveillance of hydatidiform mole is practical in a local hospital of China and could greatly improve the prognosis of post-mole neoplasia.

Multidisciplinary decision on a rectal cancer patient with multiple synchronous pulmo-nary metastasis / 中国肿瘤临床

Lungs are the second most common distant metastatic organs of colorectal cancer, following the liver. However, clinical re-searches on lung metastasis are insufficient comparing with that on liver metastasis due to its low occurrence and relatively mild bio-logical behavior. This paper aims to investigate the clinicopathological characteristics and prognostic factors of rectal cancer patients with multiple synchronous lung metastases. The patient was from the Second Affiliated Hospital of Zhejiang University, School of Medi-cine underwent multi-disciplinary diagnosis and treatment. Moreover, this article aims to discuss the related existing consensus and controversies on this issue.

Clinical study of capecitabine or S-1 as maintenance treatment to patients with advanced gastric cancer / 实用医学杂志

Objective To evaluate the efficacy and adverse effect caused by capecitabine compared with S-1 as maintenance treatment of patients with advanced gastric cancer (AGC). Methods A total of 123 AGC patients who did not suffer disease progression after first-line chemotherapy were randomized into three groups. The capecitabine group(Cap)received maintenance chemotherapy with capecitabine(1000 mg/m2 twice daily for 14 days,21 days/cycle),and the S-1 group(S1)received S-1(40,50,or 60 mg according to the body surface area and orally administered twice a day for 14 days ,21 days/cycle). The observation group was given the support-ive treatment. Patients kept this chemotherapy regimens until disease progressed or with intolerant toxicity. Re-sults The disease control rate was 70.7%in the Cap group and 80.5%in the S1 group(P=0.304). The median time of progression was 8.3 months in the Cap group and 8.5 months in the S1 group(P = 0.448). Maintenance chemotherapy groups showed better responses in the treatment group than the observation group ,which demonstrat-ed a median progression of 6.7 months(P<0.001). The median overall survival time was 15.3 months in the Cap group and 15.7 months in the S1 group(P = 0.637). Maintenance chemotherapy groups showed better responses than the observation group ,which demonstrated a median survival of 12.8 months (P < 0.05). The main side effects included hyperpigmentation,bone marrow suppression,nausea and vomiting and hand-foot syndrome. No death occurred in relation to the therapy. Conclusion The effectiveness of capecitabine and S-1 as maintenance chemotherapy in AGC patients after the first-line chemotherapy are similar,and both can prolong the time of overall survival. And the adverse reactions can be tolerated.

Impact of intensified maintenance therapy on the prognosis of children and adolescents with advanced lymphoblastic lymphoma / 中华血液学杂志

Objective@#To investigate the impact of intensified maintenance therapy on the prognosis of children and adolescents with advanced lymphoblastic lymphoma (LBL) .@*Methods@#Retrospective analysis on the treatment results of children and adolescents with stage Ⅲ and stage Ⅳ LBL who underwent BFM-NHL-90/-95 regimen without prophylactic radiotherapy. The intensified therapy group included the patients admitted from 1998 to 2005, while others were classified as the non-intensified therapy group. Patients in the intensified therapy group were intravenously treated with "etoposide phosphate plus cytrarabine" and high-dose methotrexate alternately per 2.5-3 months in addition to the oral chemotherapy with 6-mercaptopurine and methotrexate during the maintenance phase.@*Results@#A total of 187 LBL patients were enrolled. The rates of 5-year event free survival were (76.9 ± 5.8) % and (77.9 ± 4.3) % (χ2=0.249, P=0.617) respectively, in the intensified therapy (n=52) and the non-intensified therapy groups (n=135) , while the rates of 5-year overall survival of them were (78.8 ± 5.7) % and (79.8±4.1) % (χ2=0.353, P=0.552) , respectively. Stratified by stage, immunological type as well as risk stratification, the rates of long-term survival were similar between the two groups. During the maintenance phase, the rates of grade Ⅲ and Ⅳ myelosuppression in the intensified therapy and the non-intensified maintenance groups were 55.8% and 18.5%, respectively (χ2=25.363, P<0.05) .@*Conclusion@#Intensified maintenance therapy failed to improve the prognosis of patients with advanced LBL.

Clinical observation of Capecitabine versus S-1 as maintenance therapy for advanced gastric cancer after the first-line inductive chemotherapy / 中国肿瘤临床

Objective:To evaluate the efficacy and adverse reaction caused by Capecitabine compared with S-1 as maintenance treat-ments for patients with advanced gastric cancer (AGC) after first-line induction chemotherapy. Methods:A total of 130 AGC patients who did not suffer disease progression after first-line chemotherapies, including XELOX (four to six cycles), SOX (four to six cycles), and mFOLFOX6 regimen (six to eight cycles), were randomized into three groups. The Capecitabine group (Cap) received maintenance che-motherapy with Capecitabine (1 000 mg/m2 twice daily for 14 days, 21 days/cycle), while the S-1 group (S1) received S-1 (40, 50, or 60 mg according to the body surface area and orally administered twice a day for 14 days, 21 days/cycle). The control group was consid-ered as the observation group. Patients with maintenance treatments received drugs until disease progression or observation of intol-erant toxicity. Results:A total of 44, 33, and 53 patients received XELOX, SOX, and mFOLFOX6 regimens, respectively. The overall DCR was 63.1%. Among the 82 patients, 35, 28, and 19 belonged to the Cap, S1, and observation groups, respectively. The comparison be-tween the efficacy of treatments in the Cap and S1 groups did not show statistically significant differences (P=0.678). The median time of progression was 8.5 months in the Cap group and 9.0 months in the S1 group (P>0.05). Both groups showed better responses than the observation group, which demonstrated a median progression of 6.0 months (P<0.001). The median overall survivals were 14.5, 15.0, and 14.0 months in the Cap, S-1, and observation groups, respectively (P=0.188). The most common adverse effects observed among the patients with maintenance treatments included myelo-suppression, gastrointestinal reaction, fatigue, hand-foot syndrome, and stomatitis. No death occurred in relation to the therapy. Conclusion:The effectiveness of Capecitabine and S-1 as maintenance chemotherapies in AGC patients after the first-line induction chemotherapy are similar, and both can prolong the time of disease pro-gression with low toxicity.

High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer / 부인종양

OBJECTIVE: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. METHODS: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. RESULTS: In the UFT group, 103 patients (63.6%) received UFT for > or =90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). CONCLUSION: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. MATERIALS AND METHODS: Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaive, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. RESULTS: In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT's safety profile. CONCLUSION: The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC.

Insertion of Totally Implantable Central Venous Access Devices by Surgeons

PURPOSE: The aim of this study is to evaluate the results for the insertion of totally implantable central venous access devices (TICVADs) by surgeons. METHODS: Total 397 patients, in whom TICVADs had been inserted for intravenous chemotherapy between September 2008 and June 2014, were pooled. This procedure was performed under local anesthesia in an operation room. The insertion site for the TICVAD was mainly in the right-side subclavian vein. In the case of breast cancer patients, the subclavian vein opposite the surgical site was used for insertion. RESULTS: The 397 patients included 73 males and 324 females. Primary malignant tumors were mainly colorectal and breast cancer. The mean operation time was 54 minutes (18-276 minutes). Operation-related complications occurred in 33 cases (8.3%). Early complications developed in 15 cases with catheter malposition and puncture failure. Late complications, which developed after 24 hours, included inflammation in 6 cases, skin necrosis in 6 cases, hematoma in 3 cases, port malfunction in 1 case, port migration in 1 case, and intractable pain at the port site in 1 case. CONCLUSION: Insertion of a TICVAD under local anesthesia by a surgeon is a relatively safe procedure. Meticulous undermining of the skin and carefully managing the TICVAD could minimize complications.

Successful patterns of maintenance therapy in human common cancer / 国际肿瘤学杂志

Maintenance therapy is an important strategy for cancer treatment,which mainly include continuation maintenance therapy and switch maintenance therapy,with a classical model of metronomic chemo-therapy.Maintenance therapy can be an effective treatment option for patients with non-small cell lung cancer, breast cancer,colorectal cancer and ovarian cancer.

Update on the Evidence Regarding Maintenance Therapy / 결핵및호흡기질환

Maintenance therapy has emerged as a novel therapeutic paradigm for advanced non-small-cell lung cancer (NSCLC). Maintenance therapy that aims to sustain a clinically favorable state after first-line chemotherapy has two strategies. Switch maintenance therapy entails switching to a new and non-cross-resistant agent in an alternating or sequential manner, on completion of first-line chemotherapy. Continuous maintenance therapy keeps ongoing administration of a component of the current regimen after four to six cycles of chemotherapy, if there is a stable disease, or better response. Both maintenance therapies can be continued, until disease progression. The potential evidence regarding maintenance therapy includes providing the opportunity to receive additional treatment, through sustaining tumor shrinkage, and delayed emergence of tumor-related symptom. Thus far, debates over the parameters used to predict the effectiveness of maintenance therapy, financial burden, and uncertainty of improving the quality of life exist. Despite many debates, maintenance therapy, which is currently recommended, has been disclosed to be beneficial.

Second Complete Remission of Relapsed Stage IV Non-Small Cell Lung Cancer Following Retreatment / 결핵및호흡기질환

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths. Most patients were presented with advanced disease at the time of diagnosis. In advanced NSCLC, it is almost impossible to anticipate complete remission by using only cytotoxic chemotherapy or molecularly targeted agents. In our case, two patients were diagnosed as advanced NSCLC and received chemotherapy. They achieved complete response (CR). After finishing treatment, disease recurred. They were retreated with the same regimens and achieved second CR. Until now, they have received each regimen, continuously, and the CR state has been maintained.

Evaluation of the clinical efficacy of maintenance chemotherapy for local advanced non-small cell lung cancer / 肿瘤

Objective:To evaluate the clinical efficacy of maintenance chemotherapy for patients who had local advanced non-small cell lung cancer (NSCLC) and was responsive to primary radiotherapy and chemotherapy. Methods:One hundred and twenty patients with stage ⅢA or ⅢB NSCLC received 4 cycles of chemotherapy combined with radiotherapy. The 63 patients who achieved certain remission were randomly divided into maintenance chemotherapy group(n=33) and control group(n=30). The patients in maintenance chemotherapy group (treatment group) received vinorelbine (20 mg/m2, d 1 and d 8, per 28 d a cycle) and those in control group were not given maintenance chemotherapy. The clinical efficacy, survival rate and adverse reaction of the two groups were evaluated. Results:There are a longer median time to progression(TTP) in treatment group compared with control group (8.5 month vs 5.0 month, P0.05). Conclusion:Maintenance vinorelbine-based chemotherapy prolonged the median time to progression but had no effect on survival time in patients with local advanced NSCLC who responded to induction chemotherapy.