Intravenous Chemotherapy Group Research Articles

Digital subtraction angiography-guided pancreatic arterial infusion of GEMOX chemotherapy in advanced pancreatic adenocarcinoma: a phase II, open-label, randomized controlled trial comparing with intravenous chemotherapy

BackgroundAdvanced pancreatic adenocarcinoma lacks effective treatment options, and systemic gemcitabine-based chemotherapy offers only marginal survival benefits at the cost of significant toxicities and adverse events. New therapeutic options with better drug availability are warranted. This study aims to evaluate the safety and efficacy of digital subtraction angiography (DSA)-guided pancreatic arterial infusion (PAI) versus intravenous chemotherapy (IVC) using the gemcitabine and oxaliplatin (GEMOX) regimen in unresectable locally advanced or metastatic pancreatic cancer (PC) patients.Materials and methodsThis study prospectively enrolled 51 eligible treatment-naive patients with unresectable PC to receive GEMOX treatment via PAI or IVC (1:1 ratio randomization) from December 2015 to December 2019. Cycles were repeated monthly, and each process consisted of two treatments administered bi-weekly. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), 1-year survival, 6-month survival, tumor-site subgroup survival, and incidences of adverse events were compared.ResultsThe median OS of the PAI and IVC groups were 9.93 months and 10.07 months, respectively (p = 0.3049). The median PFS of the PAI and IVC groups were 5.07 months and 4.23 months (p = 0.1088). No significant differences were found in the ORR (11.54% vs. 4%, p = 0.6312), DCR (53.85% vs. 44%, p = 0.482), and 1-year OS rate (44% vs. 20.92%, p = 0.27) in PAI and IVC groups. The 6-month OS rate was significantly higher in the PAI group (100%) than in the IVC group (83.67%) (p = 0.0173). The median OS of patients in PAI group with pancreatic head and neck tumors were significantly higher than those of body and tail tumors (12.867 months vs. 9 months, p = 0.0214). The incidences of hematologic disorders, liver function disorders, and digestive disorders in the IVC group were higher than in the PAI group (p < 0.05).ConclusionGEMOX PAI therapy presented a higher 6-month OS rate and fewer adverse events than IVC in advanced pancreatic adenocarcinoma patients. Those with pancreatic head and neck tumors may yield a superior treatment outcome from PAI treatment.Trial registration numberNCT02635971.Date of registration21/12/2015.

Intravenous versus super-selected intra-arterial chemotherapy in children with advanced unilateral retinoblastoma: an open-label, multicentre, randomised trial.

Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy. This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m2] vincristine, 5 mg/kg [or 150 mg/m2] etoposide, and 18·6 mg/kg [or 560 mg/m2] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete. Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (ptrend=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis. Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma. Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.

Neoadjuvant intra-arterial versus intravenous chemotherapy in colorectal cancer.

To investigate the clinical benefits of transcatheter arterial infusion chemotherapy compared with intravenous chemotherapy in patients with colorectal cancer (CRC).From May 2013 to March 2018, 83 patients (50 men and 33 women) with surgically proven CRC were retrospectively included. Before surgery, 62 patients received conventional systemic chemotherapy, and 21 transcatheter arterial chemotherapy. Basic characteristics, disease control rate (DC), adverse reactions, postoperative complications, and toxicity profiles were collected and compared between the 2 groups.The sigmoid colon (43.37%) was the most common primary tumor location, and the least was the transverse colon (6.02%). Most lesions invaded the subserosa or other structures T3-4 (78.31%), and other lesions invaded the muscular layer T1-2 (21. 69%). The overall DC was 80.65% in the intravenous chemotherapy group and 90.48% in the arterial chemotherapy group (P < .05). Adverse events included myelosuppression and gastrointestinal reactions such as nausea, vomiting, diarrhea, abnormal liver function, and neurotoxicity, which were significantly less common in the intra-arterial group than in the intravenous group (P < .05). Postoperative complications included abdominal infection (11.29% vs 14.29%), intestinal obstruction (6.45% vs 4.76%), anastomotic bleeding (1.61% vs 0.00%), and anastomotic fistula (6.45% vs 4.76%) in the intravenous and intra-arterial groups, respectively (P > .05).Preoperative transcatheter arterial infusion chemotherapy is a safe and effective neoadjuvant chemotherapy measure for CRC with fewer adverse reactions and a higher overall DC.

Pathologic comparisons of enucleated eyes with retinoblastoma after superselective ophthalmic arterial chemotherapy with or without intravenous chemotherapy.

To describe and compare pathologic findings in eyes enucleated after superselective ophthalmic arterial chemotherapy (SOAC) or SOAC with intravenous chemotherapy (IVC) for retinoblastoma. Medical records between January 1st, 2014 and June 30th, 2017 were retrospectively analyzed, and pathologic findings were recorded. This study included 36 eyes from 22 (61.1%) male and 14 (38.9%) female patients. Nineteen of 36 (52.8%) eyes received SOAC (mean=3, range=1-7) as primary treatment, and 17 of 36 (47.2%) eyes received SOAC (mean=3.7, range=1-10) after IVC (mean=6.1, range=2-11). Tumor extension including choroidal invasion (n=9, 25%), optic nerve invasion (n=5, 13.9%) and anterior segment invasion (n=5, 13.9%) were recorded. Histopathologic evidence of ischemic damage in the retina and choroid was found in 28 (77.8%) eyes. Thrombosed blood vessels were identified in 9 (25%) eyes, including orbital artery in the retrobulbar orbit (n=1), intrascleral vessels (n=4), and chorioretinal vessels (n=6). Fibrotic changes were found in extraocular muscles (n=5, 13.9%) and optic nerve (n=5, 13.9%). Varying degrees of scleral degeneration were found in all eyes. In statistical analysis, there was no significant difference in clinical and pathologic changes between SOAC group and SOAC with IVC group except for optic nerve invasion (P=0.047). SOAC for retinoblastoma can result in ocular toxicity, and SOAC with IVC do not increase the toxicity but reduced the incidence of optic nerve invasion.

Intravenous Chemotherapy Plus Intra-Arterial Chemotherapy Versus Intra-Arterial Chemotherapy in Patients with Advanced Retinoblastoma Cancer: A Retrospective, Multicentre-Based Study

Background: Intra-arterial chemotherapy (IAC) was found to be effective for the management of advanced retinoblastoma. However, the value of the addition of intravenous chemotherapy (IVC) to IAC in advanced retinoblastoma is unclear. Methods: Kaplan-Meier analyses were performed to compare 2-year rates of ocular survival, overall survival and event-free survival between the groups. Cox proportional hazards model was used to test the independent significance of different factors. Details of enucleated eyes and their histopathological results were recorded. Findings: Between July 2008 and December 2016, 213 patients at five institutions in China with advanced retinoblastoma (group D and E eyes) were included for analysis. They were treated with IVC plus IAC (n=103) or IAC (n=110). The proportion of patients with ocular survival at 2 years was 68% (95%CI 57-76) in the IVC plus IAC group and 72% (95%CI 60-80) in the IAC group (hazard ratio [HR] 0.88 [95%CI 0.55-1.43], P=0.61).The proportion of patients with overall survival at 2 years was 97% (95%CI 92-99) in the IVC plus IAC group and 96% (95%CI 90-99) in the IAC group (HR 1.56 [95%CI 0.41-5.90], P=0.51). The proportion of patients with event-free survival at 2 years was 76% (95%CI 67-83) in the IVC plus IAC group and 79% (95%CI 69-86) in the IAC group (HR 0.96 [95%CI 0.56-1.65], P=0.89). Multivariate analyses showed eye staging and local therapy were significant prognostic factors of ocular survival. High-risk histopathologic features were identified in 10.5% (4/38) of the IVC plus IAC group and 16.7% (5/30) of the IAC group, with no statistical difference (P=0.46). Interpretation: Addition of IVC to IAC did not significantly improve survival outcomes and lower the risk of metastasis in patients with advanced retinoblastoma cancer. Longer follow-up is needed to determine long-term efficacy, but at present, additional IVC is not recommended for using outside the scope of clinical research. Funding Statement: The National Natural Science Foundation of China; the National Natural Science Foundation of Guangdong Province; the Science and Technology Planning Project of Guangdong Province; the Scientific Research General Project of Guangzhou Science Technology and Innovation Commission; and the China Postdoctoral Science Foundation. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Comparison of treatment efficacy between adjuvant intravenous chemotherapy and intravenous chemotherapy combined with intraperitoneal perfusion chemotherapy to treat postresection colon cancer.

Surgery has been the definitive treatment for locoregional colon cancer. But approximately 40% of patients died from peritoneal seeding and tumor recurrence. To prevent peritoneal recurrence, the eradication of intraperitoneal cancer cells has been critical for improving postoperative survival. This study focused on the role of IPC in postoperative treatment of colon cancer. Seventy colon cancer patients who underwent radical resection from September 2009 to September 2012 received adjuvant therapy. Specifically, 39 individuals received intravenous chemotherapy (IVC), and 31 received combined IVC and intraperitoneal perfusion chemotherapy (IVC + IPC). Disease-free survival (DFS) for those received IVC (20.71 months) was shorter than those received IVC + IPC (25.71 months). DFS in IVC group was also shorter than that in the IVC + IPC group, for patients with Stage III pathological tumor staging, T4 invasion depth, N2 lymph node metastasis, and low to undifferentiated tumor tissue. Peritoneal metastasis in the IVC + IPC group was less, but the toxicity was similar. No significant difference was observed among IPC treatment groups using three drugs. In the IVC + IPC group, DFS of patients received >5 or 3-5 times of IPC was longer than those received <3 times of treatment. No significant difference was observed in DFS between patients who received >5 times or 3-5 times of IPC. After radical resection, patients who received IVC + IPC showed prolonged DFS than those received IVC, as well as fewer peritoneal metastasis. Compared to IPC, no significantly increased side effects or complications were occurred after IVC + IPC. More work should be performed to confirm that IVC + IPC was superior to IVC for treating postresection colon cancer.

An experiment control study on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model

Objective: To compare the impact on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model. Methods: Thirty 8-weeks old female Sprague Dawley rats were randomly assigned to control group (group A, n=10), intraperitoneal chemotherapy group (group B, n=10) and intravenous chemotherapy group (group C, n=10). Cisplatin was diluted by normal saline (NS) into 4 mg/ml. On the first day of chemotherapy, 0.2 ml cisplatin dilution was injected into the abdomen of rats in group B, isodose cisplatin was injected into vein and 1.8 ml NS was injected into abdomen of rats in group C, 2.0 ml NS was injected into abdomen of rats in group A for control. Feed the three groups rats and test the anti-Mullerian hormone (AMH) in serum on day 0 (just before injection), day 10 and day 20 by ELISA, count the numble of follicle in bilateral ovaries on day 20. Results: (1) The levels of serum AMH in the three groups before and after chemotherapy were compared: ① comparison between groups: On day 10 and day 20, the AMH level in group B [(64.5±2.9), (68.6±3.4) ng/L] and group C [(76.1±4.9), (91.3±3.9) ng/L] was significantly lower than that in group A [(120.1±5.3), (121.7±4.6) ng/L; P<0.01], AMH level in group B was significantly also lower than that in group C (P=0.000). ② Comparison within groups: the AMH level on day 0 was significantly lower than that on day 10 and day 20 in group A (P<0.01), but there was no significant difference between day 10 and day 20 (P=0.427). The AMH level on day 0 was significantly higher than those on day 10 and day 20 in group B (P<0.01) and group C (P<0.01). There was no difference in AMH level between day 10 and day 20 (P=0.124) in group B, but the level was significant lower on day 10 than that on day 20 in group C (P=0.011). (2)Comparison of the number of follicles in ovaries of three groups 20 days after chemotherapy: the follicles number in group A (35±13) was greater than that in group B (16±9, P=0.003) and similar with group C (31±16, P=0.474) on day 20. The follicles number in group B was significantly less than that in group C (P=0.018). Conclusions: In the present study, both intravenous and intraperitoneal chemotherapy have impacts on ovarian reserve function and the latter might be more serious. The level of AMH will rise again over time after chemotherapy and rats undergo intravenous chemotherapy would recover faster. The results suggest that the ovarian reserve function need more time to recover after intraperitoneal chemotherapy. For patients with ovarian cancer who want to preserve fertility function, intravenous chemotherapy might be more appropriate.

First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment

PurposeThe introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes...

Outcome and prognosis of adjuvant chemotherapy of stage II colorectal cancer with lympatic invasion and stage III with N1 colorectal cancer

Purpose: Guideline of stage II colon cancer chemotherapy is controversial issue. This study aims to assist in making proper guideline of stage II colorectal cancer chemotherapy. Methods: We retrospectively analyzed the medical records of 137 patients who had colorectal cancer surgery and chemotherapy at Sanggye Paik Hospital, Surgical Department from 2008 to February 2013. We analyzed disease-free survival rate (DFS), characteristics and relationship of stage II (II), stage II with lymphatic invasion (IIL), stage III with N1 (lymph mode involvement number under 3). Results: We found new metastasis in 23 patients (liver 11, lung 5, peritoneum 6, bone 1). There is no difference in DFS between II and IIL (P=0.064). But recurrence more frequently appeared with lymatic invasion group. There is no difference in DFS between IIL and III (P=0.083). But cancer stage had not effect to recurrence (P=0.153). In IIL patients, statistically difference did not be shown between oral and intravenous chemotherapy group (P=0.500). But chemotherapy completion group had higher DFS (P=0.001). Conclusion: Between II and IIL, DFS did not have difference but low P-value. In consideration of correlation analysis result and DFS between IIL and III, we think their prognosis is not same and completion of chemotherapy influence on good outcome in stage II with lymphatic invasion colon cancer.

Enhanced anti-cancer effects of intralymphatic aclarubicin on distal lymph node metastases

The anti-cancer drug aclarubicin (2.0 mg/kg body weight) was injected into the left popliteal lymph node (the primary draining node of the foot-pad region) or into the tail vein, 8 days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells/mouse in the left hind paw foot-pad of mouse (donor). During this time, metastases were established in the lower para-aortic nodes (the secondary draining nodes of this region). On day 10, the lower para-aortic nodes taken from each donor were transferred intraperitoneally to a normal mouse (recipient). From the recipients' survival time, the viable P388 leukemia cell number in the para-aortic nodes per donor mouse was estimated with a calibration line. The recipients' survival curve in the intralymphatic chemotherapy group was statistically significantly better than that in the intravenous chemotherapy group.