The Potential Role of Tomudex in the Treatment of Advanced Colorectal Cancer

Aims and Background The quinazoline folate analog thymidylate synthase inhibitor, Tomudex, is about to enter the Italian pharmaceutical market. Its place among the therapeutic options for advanced colorectal cancer is discussed. Methods The pros and cons of currently available chemotherapeutic regimens are briefly described with special attention to patient's and tumor's determinants of treatment outcome. The mechanism of action and the results of phase I, II and III studies of Tomudex are reviewed. Results Not all patients need to be treated. Guidelines are given in this respect. Tomudex at the dose of 3 mg/m2 given i.v. every three weeks has antitumor activity similar to that of currently available regimens, with a favorable toxicity profile. Conclusions Current research approaches are unlikely to dramatically improve the treatment outcome of this disease in the near future. What can reasonably be expected is less toxicity and more convenient routes and schedules of drug administration that may translate into better quality of life for our patients. Tomudex has been devised along these lines.

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A Randomized Trial Comparing Defined-Duration With Continuous Irinotecan Until Disease Progression in Fluoropyrimidine and Thymidylate Synthase Inhibitor—Resistant Advanced Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2004.01.005 ◽

2004 ◽

Vol 22 (15) ◽

pp. 3023-3031 ◽

Cited By ~ 35

Author(s):

Rohit Lal ◽

James Dickson ◽

David Cunningham ◽

Ian Chau ◽

Andrew R. Norman ◽

...

Keyword(s):

Quality Of Life ◽

Colorectal Cancer ◽

Disease Progression ◽

Advanced Colorectal Cancer ◽

Phase Iii ◽

Random Assignment ◽

Duration Of Disease ◽

Grade 3 ◽

Synthase Inhibitor

Purpose Irinotecan given until disease progression is an accepted standard treatment for advanced colorectal cancer (CRC) resistant to fluoropyrimidines. It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control. We performed a multicenter phase III trial to compare the two policies of defined-duration versus continuous irinotecan treatment. Patients and Methods Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered. After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks, 55 patients with responding or stable disease were randomly assigned to stop irinotecan (n = 30) or continue until disease progression (n = 25). Registered patients were not randomly assigned predominantly due to disease progression (n = 236) and intolerable toxicity (n = 38). Results From the time of random assignment, there were no differences in failure-free survival (P = .999) or overall survival (P = .11) between the two arms. No difference was seen in mean global health status quality-of-life score between the two arms at 12 weeks after random assignment. No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after random assignment. Conclusion For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.

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ZD1694: A novel thymidylate synthase inhibitor with substantial activity in the treatment of patients with advanced colorectal cancer. Tomudex Colorectal Study Group.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.3.716 ◽

1996 ◽

Vol 14 (3) ◽

pp. 716-721 ◽

Cited By ~ 76

Author(s):

J R Zalcberg ◽

D Cunningham ◽

E Van Cutsem ◽

E Francois ◽

J Schornagel ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Advanced Colorectal Cancer ◽

Phase Ii Study ◽

Objective Response ◽

World Health ◽

Toxicity Profile ◽

Who Grade ◽

Synthase Inhibitor

PURPOSE Tomudex (ZD1694; Zeneca Ltd, Macclesfield, United Kingdom) appears to have a favorable toxicity profile (defined in phase I studies) and antitumor activity in a broad range of epithelial tumors. We report here the results of a large phase II study of Tomudex in advanced colorectal cancer (CRC). PATIENTS AND METHODS One hundred seventy-seven patients were entered onto the study between October 1992 and September 1993. Patients were required to have advanced CRC without prior chemotherapy (adjuvant chemotherapy was permissible) and at least one measurable lesion. Tomudex (ZD1694) was administered at a dose of 3 mg/m2 intravenously once every 3 weeks in the absence of toxicity or disease progression. Patients were assessed for objective response, progression, and survival. RESULTS Of 177 patients entered onto the study, 5% had received prior adjuvant chemotherapy and 83% had liver metastases. Objective responses were seen in 26% of patients (95% confidence interval, 19% to 33%; four complete responses [CRs] and 41 partial responses [PRs]) while median time to progression was 4.2 months and median survival 9.6 months. All sites were audited, and responses were reviewed by an independent panel. Common toxicities included mild reversible transaminitis, nausea and vomiting, and asthenia or flu-like symptoms, and World Health Organization (WHO) grade 3 and 4 leukopenia and diarrhea were seen in 6% and 9.8% of patients, respectively. Stomatitis and alopecia were common. CONCLUSION In this large multicenter phase II study of patients with advanced CRC, interesting activity was seen (objective response rate, 26%). In addition, Tomudex has an acceptable toxicity profile and a convenient dosing schedule (single intravenous injection every 3 weeks) and thus appears to offer real potential as a novel agent for the treatment of patients with advanced CRC.

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Potential Role of Cytokines in Children with Acute Appendicitis and Acute Mesenteric Lymphadenitis

Acta Chirurgica Latviensis ◽

10.2478/v10163-012-0025-5 ◽

2011 ◽

Vol 11 (1) ◽

pp. 130-133

Author(s):

Astra Zviedre ◽

Arnis Engelis ◽

Mohit Kakar ◽

Aigars Pētersons

Keyword(s):

Early Detection ◽

Acute Appendicitis ◽

Inflammatory Mediators ◽

Potential Role ◽

Clinical Symptoms ◽

Future Research ◽

Mesenteric Lymphadenitis ◽

Proper Diagnosis ◽

Near Future

Potential Role of Cytokines in Children with Acute Appendicitis and Acute Mesenteric Lymphadenitis Although, AAP and AML have different etiological factors, clinical symptoms are very much similar but treatment tactics in both the disease differ a lot. In case of AML, treatment is more conservative and does not require hospitalization while in case of AAP immediate hospitalization and maybe further surgery can be mandatory. With the identification of group of cytokines serum inflammatory mediators IL-8, IL-10, IL-12[p70], IL-17, TNF-a and MCP-1, it is believed early and proper diagnosis of AAP in the near future. Research of cytokines-serum inflammatory mediators has opened new opportunities for an early detection and differentiation of these two diseases in children.

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The prognostic role of baseline CEA and CA 19-9 values and their time-dependent variations in advanced colorectal cancer patients submitted to first-line therapy

Tumor Biology ◽

10.1007/s13277-014-2693-3 ◽

2014 ◽

Vol 36 (3) ◽

pp. 1519-1527 ◽

Cited By ~ 12

Author(s):

M. Tampellini ◽

A. Ottone ◽

I. Alabiso ◽

C. Baratelli ◽

L. Forti ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Advanced Colorectal Cancer ◽

Time Dependent ◽

Prognostic Role ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Colorectal Cancer Patients

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To Make a Choice You Should Know The Option Physiological and Psychological Contribution of the Female Component in National Security and Intelligence

Security science journal ◽

10.37458/ssj.2.1.3 ◽

2021 ◽

Vol 2 (1) ◽

pp. 36-51

Author(s):

Sabrina Magris

Keyword(s):

National Security ◽

Intelligence Community ◽

Left Behind ◽

The World ◽

Two Factors ◽

Female Component ◽

Near Future ◽

Ways Of Being

The paper addresses the importance of the role of women in Intelligence and National Security with the specific purpose to highlight the quality of female contribution in all different domains. The world is changing and in this change, Intelligence risks being left behind as never before. An epic evolution and change are underway that will upset ways of being and ways of thinking. All this not suddenly and all this without realizing it if not after the fact. The world is changing, women “are gain the upper hand” taking over also numerically and it is not realized that a change must happen in the field of Intelligence with a space left to women, not because they are women but because of their abilities. In all domains, from strategic to an operational one. Blindness to change that many Agencies are having. And those who are making changes often do so because they are obliged by the rules but not by evaluating the concrete capability of individuals. Two factors risk being explosive if no action is taken. The paper highlights the physiological and psychological contribution of the female component in the National Security and Intelligence work, and why diversity is scientifically important to successfully conduct operational and strategic tasks. It also describes the existing lack of models, how to enlarge the interest of young girls to join the Intelligence Community, and a look into the near future regarding the training and the recruitment processes with specific regards to women.

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