Purpose
To describe safety and clinical outcomes among patients with metastatic colorectal cancer (mCRC) to the liver treated with transarterial chemoembolization with HepaSphere™ Microspheres ...30–60 μm loaded with irinotecan (ΙRI-HEP-TACE).
Material and methods
In this prospective study (NCT04866290), 100 adults with confirmed mCRC to the liver who were ineligible for resection were enrolled and followed up to 24 months or death. Study outcomes among Salvage (patients not tolerating more cycles of chemotherapy) and Non-salvage patients included overall survival (OS), progression-free survival (PFS), objective response (OR), objective response rate (ORR), best tumor response (BTR), adverse events (AEs), and pharmacokinetics of irinotecan and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN38).
Results
The median age was 66 years (range: 31–89). Median OS was 15.08 months (95% confidence interval CI: 12.33–17.25). PFS was 8.52 months (95% CI: 6.0–9.0;
p
< 0.001). ORR was 42.2% (95% CI: 31.57–53.50) and 35.9% (95% CI: 25.57–47.62) based on modified RECIST (Response Evaluation Criteria in Solid Tumors) and RECIST 1.1 criteria. BTR was not significantly different between mRECIST and RECIST (
p
= 0.745). The Non-salvage group had a statistically significant difference in median OS relative to the Salvage group (15.3 vs. 3 months;
p
< 0.001). Pharmacokinetic analyses demonstrated no correlation of OS with plasma concentration of irinotecan and SN38 (all
p
> 0.05). Most AEs were Grade 2 (257/279), the most common AE was right upper abdominal pain (180/279). One major AE (tumor rupture) was reported.
Conclusion
IRI-HEP-TACE is an alternative treatment for patients with Non-salvage mCRC to the liver.
We investigated the immune profile of patients with resected Dukes' stage C colorectal cancer (CRC), receiving adjuvant therapy with edrecolomab (Mo17-1A) or first-line 5-fluorouracil (5-FU)-based ...chemotherapy.
Patients received either 5 doses of Mo17-1A over 13 weeks, or 5-FU/leucovorin, or 5-FU/levamisole over 6 and 12 months, respectively. Peripheral blood was collected postoperatively and 4 months after therapy initiation. Peripheral blood mononuclear cells were tested in the autologous mixed lymphocyte reaction (AMLR), for natural killer (NK) and lymphokine-activated killer (LAK) cell activity. Serum cytokines were quantified by ELISA.
Fifty-two patients entered the study. Postoperatively, they exhibited decreased levels of interleukin (IL)-2, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor and IL-15, low cellular immune responses (AMLR, NK- and LAK-cytotoxicity) and increased levels of IL-1beta, tumor necrosis factor-alpha, IL-6, IL-10 and prostaglandin E(2). After four months of therapy, patients receiving edrecolomab demonstrated enhanced AMLR, NK, LAK activity, increased serum levels of cytokines regulating such responses and reduced levels of acute-phase cytokines and immune suppressors, compared to patients treated with conventional chemotherapy.
Postoperative adjuvant therapy with edrecolomab restores the in vivo deficient immune responses of patients with resected Dukes' C CRC despite its clinical ineffectiveness in recent randomized adjuvant trials. These results suggest that further immunological studies with the combination of edrecolomab and chemotherapy are required.
We investigated the efficacy of Mo17-1A to improve important immunological parameters in vivo and in vitro in colorectal cancer (CRC) patients receiving no second-line treatment. Eighteen CRC ...patients stage Dukes' C were treated postoperatively with 5 doses of Mo17-1A. Peripheral blood mononuclear cells (PBMC) were analyzed for proliferative responses and cytolytic activity. Serum levels of cytokines were determined during treatment. Enhancement in the proliferative activity of patients' T cells, improvement in their lymphocytes' killing ability of natural killer (NK) and lymphokine-activated killer (LAK) sensitive tumor targets, and an in vivo increase in serum levels of interleukin (IL)-2, IL-12, IL-15, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) were noted. We conclude that treatment of CRC patients with Mo17-1A partially restores deficient cellular immune responses and the secretion of cytokines with immuno-enhancing properties. The development of novel immunotherapeutic protocols using combinations of Mo17-1A with stimuli that enhance the lytic capacity of effector cells (e.g. cytokines), may improve clinical responses in these types of patients.
This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus vinorelbine, as salvage chemotherapy in patients with metastatic breast cancer resistant to anthracyclines. Patients ...received vinorelbine (30 mg/m
2
) followed 1 hour later by full dose paclitaxel (175 mg/m
2
) every 3 weeks for a maximum of 8 cycles or until disease progression. Because of the heavy pretreatment of the patients, prophylactic granulocyte-colony stimulating factor (5 μg/kg) was administered daily for 5-10 days. To minimize potentially cumulative neurotoxicity due to both agents, amifostine was given prior to chemotherapy. Thirty-four patients: 8 with tumors primary resistant and 26 with tumors recurring within 3-6 months after anthracycline treatment, were evaluable for efficacy and toxicity. Objective responses occurred in 11 patients 32%; 95% confidence interval (CI): 16.3-47.7%), all partial responses. Responses were observed in lung and liver. The median response duration was 4 months (range 3-7), median time to progression was 5 months (range 3-9) and median overall survival was 8 months (range 4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left ventricular ejection fraction, measured and followed in 18 patients, fell less than 20% below baseline level in 9 patients (50%), but only one patient developed congestive cardiac failure. The paclitaxel-vinorelbine regimen was moderately tolerated and moderately effective in poor prognosis breast cancer patients with visceral metastases and tumors resistant to anthracyclines. The combination at these doses and schedules should be considered in the design of regimens for advanced breast cancer.
To investigate the efficacy and toxicity of gemcitabine administration followed by the combination of fluorouracil (5-FU) modulated by folinic acid in patients with advanced, symptomatic pancreatic ...cancer. The main objective was to estimate tumour response and any improvement in patients' quality of life.
The study included 48 evaluable patients with metastatic disease with no prior chemotherapy. The study duration was 3 years.
Gemcitabine 1000 mg/m(2) intravenously was given on days 1 and 8 followed by fluorouracil 350 mg/m(2) intravenously as a bolus biologically modulated by folinic acid 350 mg/m(2) intravenously given on days 1, 2, 8 and 9 in order to develop the conditions for any potential drug synergism. The regimen was administered every 3 weeks for 1 year or until disease progression.
Objective partial responses were documented in ten (21%) patients (95% CI 10.5, 35). Twenty-two (46%) patients had stable disease while 16 (33%) patients had progressive disease. The median response duration was 8 months (range 4-20). The median time to progression was 6 months (range 2-24), while the median survival of the group was 7 months (range 3-36) and the probability of surviving beyond 12 months was 20%. Of the 44 patients with tumour-related symptoms who were considered evaluable for clinical-benefit response, 28 (70%) patients had pain improvement, 25 (52%) patients had improvement of their performance status, and nine (28%) patients experienced weight gain during treatment. Serum concentrations of cancer antigen (Ca-19-9) were decreased by more than 50% in 14 (37%) of the 38 assessable patients. Chemotherapy was well tolerated, with mild myelotoxicity. Gastrointestinal toxicity was moderate with mild mucositis.
The regimen of gemcitabine and fluorouracil administered in this study was well tolerated and showed a moderate antitumour activity and a significant palliative effect on tumour-related symptoms. Because fluorouracil is a low toxicity combination agent for gemcitabine, other forms of the two-drug combination warrant further investigation.
Purpose: To evaluate the efficacy and toxicity of the FAP combination chemotherapy as first-line treatment in advanced urothelial cancer. Patients and methods: Thirty-four patients with ...histologically confirmed advanced urothelial cancer, with measurable disease and without previous chemotherapy entered the study; all 34 are evaluable. The 28 males and 6 females had a median age of 65 (19–75) and a median ECOG performance status of 1 (0–2). Twenty-eight patients had bladder cancer, four had renal pelvic cancer and two ureteral cancer. Thirty patients had transitional cell carcinoma and four mixed, mostly of grade 3. Sites of disease included lymph nodes (18), bladder (9), liver (9), pelvic mass (9), lung (7). etc. The treatment plan was as follows: 5-fluorouracil 500 mg/m2 continuous infusion D1–D5 and D22–D26; interferon-α-2b 5 million I.U./m2 D1–D5 followed by 3×/week and then D22–D26; cisplatin 25 mg/m2 D1, D8, Dl5, D22. Cycles were repeated every 36 days. Results: The median number of cycles administered was 3 (1–6). The relative dose intensities for 5-fluorouracil, interferon and cisplatin were 76%, 71% and 75%, respectively. Twenty-two of 34 patients (65%, 95% confidence interval 95% CI, 46% to 80%) had objective responses, including six complete clinical responses (CR) (18%, 95% CI, 7% to 35%) and 16 partial responses (PR) (47%, 95% CI, 30% to 65%). Three patients had stable disease and seven progressed. Two patients discontinued treatment after the first cycle because of toxicity. The median survival is 15.30 months (1.40–37.60), the median time to progression 11.60 months (4.13–37.60), and the median survival of complete responders 20.75+ months (8+ to 38+). The only significant hematologic toxicity was the grade 3–4 neutropenia in 4.4%. Non-hematologic toxic effects were unremarkable. Conclusion: The FAP combination as first-line chemotherapy is highly active in the treatment of advanced urothelial cancer, and has limited toxicity. Further phase III studies are in progress to compare FAP and M-VAC.
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