Intraluminal Chemotherapy Research Articles

Upper tract urothelial carcinoma: conservative management - intraluminal adjuvant therapy, and surveillance.

In recent years, intraluminal therapies have become a valid alternative for low grade upper tract urothelial carcinoma (UTUC) patients, as overall survival and cancer-specific survival rates were shown to be comparable to those achieved with radical nephroureterectomy for selected cases. Nonetheless, endoscopic treatment has its limitations. As technology progresses and the demand for endoscopic treatments increases, intraluminal chemotherapy and immunotherapy instillations within the upper tract have increasingly become the subject areas of research. The main intraluminal therapies and relevant instillation approaches are reviewed in this study, including recent publications and their main outcomes. The recurrence rates demonstrated in the literature strengthen the notion that patients with UTUC following current intraluminal treatments have a better prognosis than in the past. Updated relevant guidelines regarding surveillance among this population are also reviewed and summarized. The treatment of upper tract urothelial carcinoma is clinically challenging. Developments in recent years show promising results in this field and ongoing research with new developments is emerging. Further studies are required to better understand the contribution of intraluminal therapies to the management of this disease.

Advances in chemoablation in upper tract urothelial carcinoma: overview of indications and treatment patterns.

Localized upper tract urothelial carcinoma (UTUC) is a difficult disease for clinicians to treat, due to the multitude of oncological and patient factors to consider. Despite the challenges of diagnostic staging, endoscopic management, and disease recurrence, there is still a need for local therapeutic options that do not subject patients to the morbidities of radical nephroureterectomy (RNU). Intraluminal chemotherapies have allowed for improved oncological control in patients with low-grade disease receiving renal-sparing treatment approaches. This narrative review discusses the treatment modalities available for localized low-grade UTUC, with a focus on the current status of chemoablation. The OLYMPUS trial was a pivotal study that lead to the Food and Drug Administration (FDA) approval of UGN-101 (mitomycin-C) in April 2020 for the treatment of low-grade UTUC, and intraluminal chemotherapy is now a widely used modality for managing this disease. The trial reported a complete response (CR) rate of 59%, and an estimated treatment durability of 82% at 1 year. However, a concern was the reported 44% ureteral stricture rate using the retrograde approach. More research is currently underway to determine the ideal instillation method for intraluminal therapies (e.g., retrograde vs. antegrade). Lastly, we discuss upcoming treatment options. Newer novel agents like padeliporfin vascular targeted photodynamic (VTP) therapy (brand name TOOKAD) are currently being studied, which will in hope provide additional treatment options for UTUC patients.

577P - Intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): A randomized, multicenter, prospective, phase III trial

BackgroundWhether colorectal cancer patients who undergo radical resection can benefit from intraoperative chemotherapy is still under debate. Therefore, we aimed to compare the results of intraoperative chemotherapy combined with radical surgical resection with surgical resection alone in colorectal cancer patients. MethodsThis is a multicenter, open-label, randomized, non-inferiority, phase 3 trial. All patients who had been histologically confirmed and could receive radical resection with no sign of distance metastasis, were enrolled. The patients were randomized to receive intraoperative chemotherapy with radical surgical resection, or radical surgery resection alone (1:1). Intraoperative chemotherapy included portal vein chemotherapy (200mg/m2 5-FU), intraluminal chemotherapy (1000mg/m2 5-FU), and intraperitoneal chemotherapy (300mg/m2 5-FU). The primary endpoint was 3-year disease-free survival (DFS) analyzed on an intention-to-treat basis with an α of 0.05 and a power of 80%. ResultsFrom January 2011 to January 2016, 685 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy with radical surgical resection (n=341), or surgical resection alone (control group, n=344). After a median follow-up of 65.1 months, 21 patients in the intraoperative chemotherapy group and 26 patients in the control group had died. 39 patients in the intraoperative chemotherapy group and 47 patients in the control group experienced distance metastasis or local recurrence. Intraoperative chemotherapy showed no significant benefit for colorectal cancer patients who underwent radical resection (p=0.334). Subgroup analyses showed that patients with pre-treatment abnormal CEA level (> 5ng/ml) could benefit from intraoperative chemotherapy (p=0.026, HR:0.516). The patients with pre-treatment normal CEA level (< 5ng/ml) still did not benefit from intraoperative chemotherapy (p=0.298). ConclusionsIntraoperative chemotherapy could improve 3-years DFS of colorectal cancer patients whose pre-treatment serum CEA level was higher than 5ng/ml. Clinical trial identificationNCT01465451. Legal entity responsible for the studyZhizhong Pan. FundingSun Yat-sen University 5010 funding. DisclosureAll authors have declared no conflicts of interest.

Effects of intraluminal chemotherapy on colorectal cancer – study in an orthotopic murine model

Effects of intraluminal chemotherapy on colorectal cancer – study in an orthotopic murine model

Comparing the effect of adjuvant chemotherapy by portal vein infusion with intraluminal chemotherapy for colorectal cancer

To compare the effect of 5-fluorouracil (5-FU) portal vein infusion (PVI) for 7 days after radical resection, with intraluminal chemotherapy during operation for eliminating liver metastasis and elevating long-term prognosis in colorectal cancer. 162 colorectal cancer patients with radical resection were divided into portal vein chemotherapy group (group A, 82 cases) and intraluminal chemotherapy group (group B, 80 cases) randomly. In group A, 5-fluorouracil were infused with 1g per day constantly for 7 days after operation through portal vein catheters, which placed into greater omental vein and fixed on the abdominal wall. In group B, intraluminal chemotherapy was given and 5-fluorouracil 0.5 g was injected into the greater omental vein during operation. The short-term complications and long-term effect in the two groups were compared by statistical software SPSS 8.0. Group A had more operative complications, and no statistical differences was found in hospital time and survival rate of the two groups. The 5-year survival rate is 76.7% (group A: 74.3%, group B: 79.2%), and the liver metastasis rate is 19.8%. There is no significant difference between the two group-survival curves. Multiple variable analysis suggested that Dukes' stage was the prognosis factor (P < 0.05). The present study demonstrated that the two chemotherapy methods play an important role in preventing liver metastasis and improving the survival rate, and the intraluminal chemotherapy would be easier and simpler. The result should be further improved by using combined chemotherapy.

Regional Chemotherapy Using Continuous Intravesical Infusion Doxorubicin for the Treatment of Muscle Invasive Transitional Cell Bladder Carcinoma in a Rat Model

Previously established animal models of invasive transitional cell bladder carcinoma and continuous infusion intravesical drug delivery were combined to evaluate the urothelial toxicity and antineoplastic efficacy of continuous intravesical infusion doxorubicin (DOX).Dose-response toxicity experiments studied histologic changes in the rat urinary bladder following urothelial exposure to three different urinary levels of DOX, as a function of the duration of drug infusion. Systemic and local drug absorption, as measured by DOX levels in serum, bladder, retroperitoneal lymph nodes, and liver, was measured at intervals during drug administration. In vitro chemosensitivity assays were used to determine tumor sensitivity to DOX. Treatment studies evaluated the impact of 14-day continuous infusion DOX beginning seven days following tumor implantation.No histologically discernable changes in the normal urothelium were noted in bladders of animals receiving continuous intravesicle DOX at mean urinary concentrations of 0.05μg./mL (n = 5), 0.56μg./ml (n = 10), and 5.69μg./ml. (n = 10) for periods of up to 14 days. Serum drug concentrations demonstrated a non-significant upward trend following the start of therapy. Significant increases in tissue DOX levels were noted in the bladder and retroperitoneal lymph nodes on chemotherapy days 7 and 14. Mean tissue DOX concentrations in both the bladder and lymph nodes were greater than the IC50 observed in the in vitro sensitivity assay. DOX-treated tumor-bearing animals (n = 17) had a mean tumor volume (±standard deviation) of 0.65gm. ± 0.52gm. compared to an average tumor volume of 1.20gm. ± 0.66gm. in the control group (n = 18) (p = 0.0112).Continuous infusion intraluminal chemotherapy demonstrated a clear cytoreductive effect with minimal local toxicity in this model. Drug tissue levels were observed in regional lymphatic drainage fields as well as the bladder wall. Further study to evaluate this approach as a bladder-sparing alternative to muscle invasive disease is warranted.

Bladder hyperthermia in the treatment of vesical papillomatosis.

22 cases of multiple low-stage bladder tumours were treated with intraluminal chemotherapy (Thio-Tepa) and bladder hyperthermia. Hyperthermia seemed to enhance the local cytotoxicity of Thio-Tepa in the bladder which is favourable in increasing cytostatic efficacy at the tumour site without increased systemic toxicity. Tumour responses (total and partial) amounted to nearly 50% of the treated cases. This technique thus fails to offer substantial gains in the therapy of vesical papillomatosis due to a high rate of local complications.

Adjuvant chemotherapy with 5-fluorouracil in surgery for colorectal cancer: eight-year progress report.

An eight-year progress report of a method of intraluminal chemotherapy adjuvant to operation for cancer of the colon and rectum is presented. The technic involves sequestering the diseased segment between tape ligatures. A cancericidal drug is injected into the lumen within the taped area. The clamping of the pedicle vessels is deliberately delayed 30 minutes to allow maximal absorption of drug. In the 5-FU-treated group, the agent is also injected intravenously on postoperative days 1 and 2. Seventy-seven patients (excluding four postoperative deaths) in the treated series were followed for as long as eight years. No significant increase in morbidity or mortality was associated with this technic. Follow-up studies of 5-FU-treated patients with Stage III cancers (positive mesenteric nodes) indicate that the trend toward increased survival of Stage III patients noted at five years continues to be sustained at eight years.

A five year progress report on the effectiveness of intraluminal chemotherapy (5-fluorouracil) adjuvant to surgery for colorectal cancer

1. 1. Nationwide survival rates after surgery for cancer of the colon and rectum have not improved in the past twenty years. 2. 2. The modes of spread of cancer of the colorectum are now well known. 3. 3. A new combined surgical, intraluminal, and systemic chemotherapy regimen has been evolved in our clinic, hopefully to inhibit tumor spread along these pathways and thus enhance survival rates. 4. 4. A five year clinical experience using 5-FU intraluminally and systemically has been computer-analyzed. 5. 5. No apparent improvement in survival rates in stage I and II cases (negative nodes) was indicated in the 5-FU treated group versus nationwide averages. 6. 6. In the positive node group (stage III) the most significant improvement seemingly develops. At five years the cumulative proportion survival rate is 65 per cent for the 5-FU treated group versus 32 per cent in the nationwide (control) series and 26 per cent in the St. Vincent's Hospital (control) series. 7. 7. This is only a probing study. The authors well recognize the statistical pitfalls of such a small series of cases in a single institution. 8. 8. Hopefully a multihospital cooperative project with a double blind randomized study design may be achieved, utilizing upwards of 150 cases yearly.

Adjuvant intraluminal chemotherapy with 5-fluorouracil in simulated colon cancer in the rat.

Adjuvant intraluminal chemotherapy with 5-fluorouracil in simulated colon cancer in the rat.

Intraluminal chemotherapy adjuvant (HN2 or 5-FU) to operation for cancer of the colon and rectum. Follow-up report of 83 cases.

Intraluminal chemotherapy adjuvant (HN2 or 5-FU) to operation for cancer of the colon and rectum. Follow-up report of 83 cases.

Intraluminal chemotherapy with nitrogen mustard in simulated cancer of the colon in the rat

Summary o 1. Implantation of Walker 256 carcinosarcoma in the cecal pouch of the rat has produced a simulated cecal cancer. 2. Intraluminal use of HN2 as an adjuvant to resection of the cecal pouch Walker 256 carcinosarcoma in the rat has resulted in a reduction from 42 per cent to 20 per cent in the incidence of local suture line recurrence.