A comparative theoretical study on the interaction of pure and carbon atom substituted boron nitride fullerenes with ifosfamide drug

Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB) in Indian patients using Cisplatin and Etoposide combination chemotherapy Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v20) Results: Forty patients were available for final evaluation Median age of presentation of patients was fifty-six years Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease Anemia was the most common hematological toxicity observed (seen in 81% of patients) Nausea and vomiting were the most common non -hematological toxicity seen Sensory neuropathy was seen in 38%of patients 88% patients developed alopecia Seven patients developed febrile neutropenias Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen

/pdf/chemotherapy-related-toxicity-in-locally-advanced-non-small-41sj7ncbxv.pdf

Chemotherapy related toxicity in locally advanced non-small cell lung cancer.

Pharmaceuticals sterilized by electron beam irradiation, i.e., flutamide (FA), ifosfamide (IA) and aminoglutethimide (AA), applied in anticancer therapy, were studied in order to determine the kinetics of the radical decay and to find out the structure of some intermediates. Two species identified in flutamide were assigned to a more stable tertiary carbon-centred radical and a less stable aryl radical or nitrogen-centred radical cation. Two components were found in ifosfamide, one belongs to the radical formed on the loss of chlorine atom and another reveals a broad anisotropic signal of hyperfine interaction, a(1P) = 5.3 mT, together with a narrow splitting of 0.7 mT due to unassigned protons. Radiation generates in aminoglutethimide two different, highly populated radical pairs that rearrange in time into more stable radicals. Electron-beam radiolysis induced slightly more paramagnetic species in AA than in IA and about 20 times less than in FA. On a long time scale the decay rates of radicals in irradiated samples increase successively as AA<FA<IA.

Radical decay in irradiated drugs: Flutamide, ifosfamide

The integration of chemotherapy, radiation therapy (RT), and surgery in the management of patients with stage IIIA (N2) non-small-cell lung carcinoma is challenging. The American College of Radiology (ACR) Appropriateness Criteria Lung Cancer Panel was charged to update management recommendations for this clinical scenario. The Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. There is limited level I evidence to guide patient selection for induction, postoperative RT (PORT), or definitive RT. Literature interpretation is complicated by inconsistent diagnostic procedures for N2 disease, disease heterogeneity, and pooled analysis with other stages. PORT is an appropriate therapy following adjuvant chemotherapy in patients with incidental pN2 disease. In patients with clinical N2 disease who are potential candidates for a lobectomy, both definitive and induction concurrent chemotherapy/RT are appropriate treatments. In N2 patients who require a pneumonectomy, definitive concurrent chemotherapy/RT is most appropriate although induction concurrent chemotherapy/RT may be considered in expert hands. Induction chemotherapy followed by surgery +/- PORT may also be an option in N2 patients. For preoperative RT and PORT, 3-dimensional conformal techniques and intensity-modulated RT are most appropriate.

ACR appropriateness criteria ® induction and adjuvant therapy for N2 non-small-cell lung cancer

Background : Lung cancer is the most common cancer in the world accounting for 17.6% cancers worldwide. The AAR in Indian population varies from 0.98-15.55. The aim of the present study was to analyze a reduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and III B) using Wobe Mugos E and its evaluation using micronuclei as a cytogenetic marker. Micronuclei, which are cytoplasmic fragments of DNA, have been used as a biological dosimeter to assess DNA damage. Material and Methods : Fourty patients of locally advanced NSCLC were randomized into two study groups between 2001-2003. One group received neoadjuvant chemotherapy using Cisplatin and Etoposide. The other group received neoadjuvant chemotherapy using Cisplatin and Etoposide along with Wobe Mugos E which is a proteolytic enzyme preparation. A study of micronuclei frequency was done pre and post chemotherapy in both groups. Results : Thirty eight patients were available for final evaluation. Anemia was the most common hematological toxicity observed. Nausea and vomiting were the most common non -hematological toxicity seen. Wobe Mugos E was found to reduce the incidence of leucopenia (p = 0.005), nausea (p=0.004), vomiting (p= 0.003) , sensory neuropathy ( p = 0.032 ) and treatment related depression (p= 0.005). A reduction in micronuclei was seen in patients in patients on Wobe Mugos E. (p =0.01). Conclusion : Neo-adjuvant chemotherapy related acute toxicity is a major problem in patients with advanced lung cancer. A reduction in micronuclei frequency shows Wobe Mugos E to be effective in reducing chemotherapy related acute toxicity. ©

Micronuclei evaluation of reduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer: an indian experience.

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m−2 and mesna 750 mg m−2 two times a day, cisplatin 25 mg m−2 and etoposide 100 mg m−2, all administered intravenously (i.v.) on days 1–3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3–4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3–34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1–54+). Median OS for the entire group was 12.5 months (range 2–57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series. © 1999 Cancer Research Campaign

/pdf/ifosfamide-cisplatin-and-etoposide-combination-in-locally-2cwnlnm844.pdf

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study.

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Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study.