BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

OBJECTIVE: To evaluate the clinical efficacy and safety of domestic imatinib (made in China) in patients with newly diagnosed chronic myeloid leukemia chronic phase(CML-CP). METHODS: Fifty-seven newly diagnosed CML-CP patients who did not receive any other anti-CML treatment were treated by domestic imatinib 400 mg once a day. The hematological, cytogenetic and molecular reactions and safety were observed and evaluated after 3, 6 and 12 months of treatment. RESULTS: Fifty-six patients were treated for ≥3 and 6 months, among which 50 patients were treated for ≥12 months. After 3 months of treatment, 49 patients underwent hematological examination, 47 patients (95.9%) achieved complete hematological response (CHR), 49 patients underwent cytogenetic examination, 39 patients (79.6%) achieved major cytogenetic response (MCyR), and 12 patients (24.5%) achieved complete cytogenetic response (CCyR). 49 patients underwent the level of BCR-ABL test, including 41 patients (83.7%) with BCR-ABL CONCLUSION In the real world, Domestics imatinib mesylate is effective and safe in the treatment of newly diagnosed CML-CP patients, but long-term follow-up data are still necessary to verify its long-term efficacy.
Antineoplastic Agents/therapeutic use* ; Benzamides/therapeutic use* ; China ; Fusion Proteins, bcr-abl/genetics* ; Humans ; Imatinib Mesylate/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Piperazines ; Pyrimidines/therapeutic use* ; Treatment Outcome

OBJECTIVE: To evaluate the clinical effect of filiform fire needling on moderate and severe pain in advanced cancer. METHODS: A total of 66 patients with moderate and severe pain in advanced cancer were randomly divided into an observation group (34 cases, 4 cases dropped off) and a control group (32 cases, 2 cases dropped off). The two groups were treated with oral analgesics continuously for 4 weeks. The moderate pain patients was given bucinnazine hydrochloride tablets (starting at 30 mg, once every 6 hours, increasing by 30%-50% until the titration volume was reached), and the severe pain patients were given oxycodone hydrochloride sustained-release tablets (starting at 20 mg every 12 hours and increasing by 25%-50% until the titration volume was reached). The observation group was cooperated with filiform fire needling at point, Zusanli (ST 36), Liangqiu (ST 34), Qihai (CV 6), Guanyuan(CV 4), Quchi (LI 11) and Waiguan (TE 5) once every other day for 4 weeks. The changes of numerical rating scales (NRS) scores were observed in both groups before and after treatment, and the amount of analgesics and the incidence of adverse reactions were recorded. The clinical effects in the two groups were evaluated. RESULTS: The effective rate was 90.0% (27/30) in the observation group, which was higher than 66.7% (20/30) in the control group (<0.05). After treatment, the NRS scores of both groups were lower than those before treatment (<0.05), and the reducing degree in the observation group was larger than that in the control group (<0.05). The average dosage of bunarizine hydrochloride tablets and oxycodone hydrochloride sustained release tablets to titration volume in the observation group was less than that in the control group (<0.05). The incidence of adverse reactions was 23.3% (28/120) in the observation group, which was lower than 44.2% (53/120) in the control group (<0.05). CONCLUSION Filiform fire needling can alleviate pain symptoms of patients with moderate and severe pain in advanced cancer, reduce the amount of analgesics, and decrease the incidence of adverse reactions.
Acupuncture Points ; Acupuncture Therapy ; Analgesics ; therapeutic use ; Cancer Pain ; therapy ; Humans ; Neoplasms ; complications ; therapy ; Oxycodone ; therapeutic use ; Pain Management ; Piperazines ; therapeutic use ; Treatment Outcome

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Brain Edema ; drug therapy ; etiology ; Brain Injuries, Traumatic ; complications ; drug therapy ; Gene Expression Regulation, Enzymologic ; drug effects ; Indazoles ; pharmacology ; therapeutic use ; MAP Kinase Signaling System ; drug effects ; Matrix Metalloproteinase 9 ; genetics ; Piperazines ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the feasibility of imatinib reintroduction in gastrointestinal stromal tumor(GIST) with high recurrence risk after imatinib adjuvant therapy failure.

METHODSClinical and follow-up data of 24 recurrent GIST patients with high recurrence risk receiving imatinib standard dose reintroduction(400 mg/d or 600 mg/d) after stopping imatinib adjuvant treatment more than 3 months in Department of GI Oncology of Peking University Cancer Hospital from August 2005 to January 2016 were retrospectively analyzed. The objective response rate(ORR), relapse-free survival(RFS) of imatinib reintroduction were evaluated and the difference of efficacy in patients receiving different imatinib adjuvant therapy duration were compared.

RESULTSOf 24 patients, 21 were male and 3 were female. The median age was 53 years(39-72 years). Mutation detection of tumor tissues before imatinib therapy showed 20 patients had c-Kit exon 11 mutation,3 patients exon 9 mutation and 1 patient c-Kit/PDGFRA wild type mutation. The median recurrence time was 14 months in all the patients (95%CI:7.9-20.0) and in those patients receiving imatinib adjuvant therapy for 1 or 2 years (9 patients in each group, 95%CI:11.1-16.9 and 8.2-19.8 respectively). The median recurrence time of 3 patients receiving imatinib adjuvant therapy for 3 years was 24, 41 and 54 months respectively. Of 2 patients receiving imatinib adjuvant therapy for 5 years, the median recurrence time was 4 and 18 months. Only one patient received imatinib adjuvant therapy for 6 years, and the recurrence time was 6 months. Twenty patients with exon 11 mutation and 1 patient with wide type received imatinib treatment at a dose of 400 mg daily, and 3 patients with exon 9 mutation received the dosage of 600 mg per day. Among the patients receiving imatinib reintroduction, 11 patients(45.8%) got partial response(PR), 12 patients(50.0%) had stable disease and 1 patient had progression disease. The response rate in patients receiving imatinib adjuvant therapy for 1 year(6/9, 67%) was significantly higher than that in patients receiving adjuvant therapy for ≥2 years(3/15, 20%)(P=0.036). The median progression-free survival (PFS) of imatinib reintroduction was 31 months in all the patients(95%CI:23.6-38.4). The median PFS in patients receiving imatinib adjuvant therapy for 1 year(9 cases), 2 years (9 cases) and ≥3 years (6 cases) was 50 months(95%CI:27.3-72.7), 26 months(95%CI:10.7-41.3) and fall short of median PFS. No significant difference was observed among three groups(P=0.295).

CONCLUSIONSImatinib reintroduction is still effective to GIST after imatinib adjuvant therapy failure. The different imatinib adjuvant therapy duration can influence the benefit of imatinib reintroduction.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Disease-Free Survival ; Exons ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; Humans ; Imatinib Mesylate ; therapeutic use ; Male ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local ; Piperazines ; Pyrimidines ; Retrospective Studies

OBJECTIVETo investigate the efficacy of targeted therapy combined with surgery in the treatment of recurrent and metastatic gastrointestinal stromal tumor(GIST).

METHODSClinicopathological and followed-up data of 318 patients with recurrent and metastatic GIST admitted in Zhongshan Hospital between January 2000 and December 2015 were analyzed retrospectively. According to different treatment methods, the patients were divided into four groups: surgery group (operation alone, 44 cases), target therapy group (imatinib alone, 108 cases), target therapy combined with surgery group (imatinib plus operation, 139 cases), other therapy group (chemotherapy, Chinese medicine and others, 27 cases). The progression-free survival (PFS) and overall survival (OS) of four groups were compared.

RESULTSThe baseline informations, such as age, gender, primary site, et al, were not significantly different (all P>0.05), but the recurrent and metastatic site was significantly different among 4 groups (P=0.000). The medial PFS of surgery group, target therapy group, target therapy combined with surgery was 16(95%CI: 4.9 to 27.0) months, 44 (95%CI: 30.9 to 57.1) months, 35 (95%CI: 26.5 to 43.5) months, respectively, and the latter 2 groups had significantly longer PFS than surgery group(P=0.000), while no significant difference was found between target therapy group and target combined with surgery group (P=0.251). The median OS of surgery group, target therapy group, target therapy combined with surgery, and other therapy group was 24 (95%CI: 9.0 to 39.0) months, 69(95%CI: 40.8 to 97.2) months, 92(95%CI: 78.0 to 106.0) months, 12(95%CI: 9.5 to 14.5) months. Target therapy group and target therapy combined with surgery group had significantly longer OS than surgery and other therapy groups (P=0.000), while the target therapy combined with surgery group had significantly longer OS than target therapy group(P=0.028).

CONCLUSIONTarget therapy combined with surgery can prolong the survival of recurrent and metastatic GIST patients.

Antineoplastic Agents ; therapeutic use ; Benzamides ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; pathology ; surgery ; Humans ; Imatinib Mesylate ; therapeutic use ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Retrospective Studies

Besides 36 (28 single-tablets and 8 fixed-dose combinations) used antiretroviral drugs clinically, there are a number of investigational antiretroviral agents currently in phase 2-3 clinical trial. Tenofoviralafenamidefumarate (TAF) is a novel nucleoside analogue reverse transcriptase inhibitor that is potent and less toxicity than tenofovir (TDF). Doravirine is a non-nucleoside analogue reverse transcriptase inhibitor that demonstrates activity against NNRTI-resistant viral strains. GSK744 is an integrase inhibitor with a long acting preparation. In addition, several drugs with new mechanisms are also noted, for example, BMS-663 068 is a small molecule CD4 attachment inhibitors and cenicriviroc is a novel CCR5/CCR2 antagonist with antiretroviral activity and anti-inflammatory effects. Several drug classes that target known pathways in HIV latency have being developed, and leading the list are histone deacetylase inhibitors. Other agents include protein kinase C activators, positive transcription elongation factor activators, DNA methyl-transferase inhibitors and histone methyl-transferase inhibitors and so on. This review is focused on the above-mentioned drug candidates that may be used in clinical in next couple of years and those compounds that can reverse latent HIV infections.
Adenine ; analogs & derivatives ; therapeutic use ; Anti-HIV Agents ; therapeutic use ; HIV Infections ; drug therapy ; Humans ; Organophosphates ; therapeutic use ; Organophosphonates ; therapeutic use ; Piperazines ; therapeutic use ; Pyridones ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use ; Tenofovir

OBJECTIVETo evaluate the efficacy of imatinib mesylate (IM) for patients with newly diagnosed chronic myeloid leukemia (CML) and patients after failure of Recombinant Human interferon-α2b (IFN-α2b) therapy.

METHODSA total of 86 patients with CML in chronic-phase, including 61 newly diagnosed cases and 25 cases of IFN-α2b failure, who received IM at 400 mg daily were retrospectively analyzed. Conventional cytogenetic analysis of R-banding was used to detect chromosome abnormalities and real-time PCR was used to detect BCR-ABL fusion gene.

RESULTS81.9% of newly diagnosed patients and 36.0% of IFN-α2b failure patients achieved partial cytogenetic response (PCyR) by 6 months. In addition, 86.9% of newly diagnosed patients and 68.0% of IFN-α2b failure patients achieved complete cytogenetic response (CCyR) in 24 months. There was significant difference between two groups (P<0.001). The median time achieved CCyR in newly diagnosed group and IFN-α2b failure group were 6 months and 15 months, respectively. Compared with newly diagnosed group, IFN-α2b failure group showed lower rate of complete molecular remission (CMR) (70.4% vs 40.0%, P=0.033). There are 14 patients (22.9%) in newly diagnosed patients with cytogenetic resistance, among whom 4 with primary cytogenetic resistance; while there were 14 patients (56.0%) in IFN-α2b failure group with cytogenetic resistance, all of whom with primary resistance.

CONCLUSIONCompared with newly diagnosed patients, CML patients after failure of IFN-α2b therapy have a high rate of primary cytogenetic resistance and low response rate to IM.

Benzamides ; therapeutic use ; Humans ; Imatinib Mesylate ; Interferon-alpha ; therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Retrospective Studies ; Treatment Failure ; Treatment Outcome

OBJECTIVE: We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. MATERIALS AND METHODS: In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. RESULTS: The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. CONCLUSION: Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*adverse effects/therapeutic use ; Ascites/pathology/radiography ; Benzamides/*adverse effects/therapeutic use ; Echocardiography/methods ; Edema/pathology/radiography ; Female ; Gastrointestinal Stromal Tumors/drug therapy/pathology/*radiography ; Gastrointestinal Tract/pathology/*radiography ; Heart Failure/radiography ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy/*adverse effects ; Pericardial Effusion/pathology/radiography ; Peritoneal Neoplasms/diagnosis/radiography/secondary ; Piperazines/*adverse effects/therapeutic use ; Pleural Effusion/pathology/radiography ; Pyrimidines/*adverse effects/therapeutic use ; Radiology ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo study the effect of urapidil combined with phentolamine in the management of hypertension during extracorporeal circulation.

METHODSNinety patients undergoing aortic and mitral valve replacement were randomly divided into 3 equal groups to receive treatment with phentolamine (group A), urapidil (group B), or both (group C) during extracorporeal circulation. The mean arterial pressure (MAP) before and after drug administration, time interval of two administrations, spontaneous recovery of heart beat after aorta unclamping, ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, post-parallel cycle time, dopamine dose after cardiac resuscitation, and perioperative changes of plasma TNF-α and IL-6 levels were recorded.

RESULTSThere was no significant difference in MAP between the 3 groups before or after hypotensive drug administration (P>0.05). The time interval of two hypotensive drug administrations was longer in group C than in groups A and B (P<0.05). The incidence of spontaneous recovery of heart beat after aorta unclamping, incidence of ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, and post-parallel cycle time were all comparable between the 3 groups. The dose of dopamine administered after cardiac resuscitation was significantly larger in group B than in groups A or group C (P<0.05). The plasma levels of TNF-α and IL-6 were significantly increased after CPB and after the operation in all the groups, but were lowed in group C than in groups A and B at the end of CPB and at 2 h and 12 after the operation.

CONCLUSIONSUrapidil combined with phentolamine can control hypertension during extracorporeal circulation without causing hypotension.

Extracorporeal Circulation ; Heart Rate ; Humans ; Hypertension ; prevention & control ; Interleukin-6 ; blood ; Phentolamine ; therapeutic use ; Piperazines ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood