Chemotherapy anthracyclines

Cytarabine is used in the chemotherapy of acute myelogenous leukemia, usually in combination with anthracyclines, thioguanine, or both. It is less useful in acute lymphoblastic leukemia and lymphomas and has marginal activity against other tumors. Myelosuppres-sion is a major toxicity, as is severe bone marrow hypoplasia nausea and mucositis may also occur. 

Each category of chemotherapy drugs has similar side effects. Anthracyclines cause cardiac toxicity, which is related to the cumulative dose. Tubulin interactive agents are associated with neuropathy and ileus. Alkylating agents are associated with secondary malignancies. 

Clinicians should play a role in chemotherapy safety, patient education, and monitoring patient response to therapy. For example, cumulative doses of anthracyclines should be monitored along with signs and symptoms of heart failure. Clinicians also should monitor concurrent medications along with chemotherapy for drug interactions. 

The taxanes (e.g., paclitaxel and docetaxel) are a newer class of agents that rival the anthracyclines in their activity in metastatic breast cancer, becoming (arguably) the most active class of chemotherapy for this disease. 

The goal of induction chemotherapy in AML is essentially identical to that in ALL Empty the bone marrow of all hematopoietic precursors, and allow repopulation with normal cells. The combination of an anthracycline (e.g., daunorubicin, doxorubicin, or idarubicin) and the antimetabolite cytarabine forms... 

Older adults are not as tolerant of or as responsive to remission induction and consolidation chemotherapy as younger patients. Younger adults treated with a standard induction regimen of an anthracycline and cytarabine have approximately 70% probability of attaining a CR, whereas patients older than 60 years of age have only a 38% to 62% probability. Further, long-term survival for patients older than 60 years is only 5% to 15% compared with 30% DFS for younger adults.9... 

Platinum complexes are cytotoxic agents yet the paradigm in cancer chemotherapy has moved to a more targeted approach, with special emphasis on signaling pathways. In this respect a remarkable story is that of arsenic trioxide, As203 (Trisenox, Cell Therapeutics Inc, Seattle, USA) which was approved by the FDA in September 2000 for treatment of acute promomyelo-cytic leukemia (APL) in patients who have relapsed or are refractory to retinoid and anthracycline chemotherapy. An estimated 1,500 new cases of APL are diagnosed yearly in the US, of which an... 

Dexamethasone 20 mg IV 30 minutes before chemotherapy during anthracycline therapy... 

Primary chemotherapy with either an anthracycline- or taxane-containing regimen is recommended. The use of trastuzumab with chemotherapy is appropriate for patients with HER2-positive tumors. 

Epirubicin — Anthracyclines have been used in cancer chemotherapy for more than 30 years and epirubicin (EPI) is one of the most widely used agents.55 Li et al. developed a high-throughput method for the analysis of epirubicin in human plasma using UPLC-MS/MS.56 A Waters Acquity UPLC system was coupled with a Micromass Quattro Premier MS. The stationary phase was a Waters Acquity BEH C18 column (50 x 2.1 mm, 1.7 jum). The column was maintained at 30°C. Solvent A was 0.1% formic acid in water and solvent B was acetonitrile. The mobile phase was delivered at a flow of 0.20 mL/min in a step gradient mode at 85% solvent A at 0 min, 70% solvent A at 1.00 min, and 85% solvent A from 2.50 to 4.00 min. Epidaunorubicin (EPR) was the IS. 

Finally, one of fhe most recent and most interesting approvals of a new formulation of paclifaxel was fhe approval of the agent ABl-007 (Abraxane ) (Abraxis Oncology, Schaumburg, IL, U.S.A.) (paclifaxel protein-bound particles for injectable suspension [albumin-bmmd]). It is indicated for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. The endpoint for that pivotal trial of Abraxane vs. paclitaxel was a... 

Daunorubicin is an anthracycline antibiotic used in chemotherapy. It is diluted with infusion fluid to a concentration of 1 mg/mL and given over 20 minutes to reduce the occurrence of irritation. A liposomal formulation is also available. 

Liposome-encapsulated immunomodulators are currently under investigation in different patient groups although this development has certainly not advanced as far as that with the liposomal anthracyclines. MLV-MTP-PE (multilamellar vesicles-muramyl tripeptide-phos-phatidylethanolamine) was studied in several clinical trials in osteosarcoma patients who developed pulmonary metastases during adjuvant chemotherapy [108], The intravenous administration of MLV-MTP-PE induced tumouricidal properties in monocytes as well as increase in serum IL-1 shortly after intravenous infusion. Furthermore elevations in C-reactive protein, 32-microglobulin and ceruloplasmin were frequently observed. Even higher anti-tumour activity was observed in combination with ifosfamide. These preliminary results suggests that liposome-encapsulated immunomodulators in combination with chemotherapy may be an appropriate treatment for recurrent disease. 

Campone M, Cortes-Funes H, Vorobiof D, et al, Vinflunine A new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy, Br J Cancer 95 1161-1166, 2006. 

Kaufman PA. Paclitaxel and anthracycline combination chemotherapy for metastatic breast cancer. Semin Oncol 1999 26(3 Suppl 8) 39-46. 

Contemporary Phase I-Ii Trials of Primary Anthracycline-Based Chemotherapy, Followed by Surgery and Radiation... 

Thomas E, Buzdar A, HortobagyiG, etal. Long-Term Follow Up of Stage III Breast Cancer-Combined Modality Treatment with Anthracycline Containing Chemotherapy (CT) The MD Anderson Experience (Meeting abstract). ProcAnnu Meet Am Soc Clin Oncol 1999 18 A284. 

Hodgkin s disease accounts for 1% of all new cancers diagnosed in Western countries and for 15% of all malignant lymphomas. In patients with early stage lA-IIA disease without B-symptoms or bulky adenopathy, therapy consists of either extended field radiotherapy or limited duration chemotherapy, e.g. ABVD (anthracycline, bleomycin, vinblastine, dacarbazine) for 3-4 cycles followed by involved field radiotherapy. Radiation alone results in a 10-year relapse free survival of 70-75% and, because of the efficacy of salvage chemotherapy for those who relapse, an overall survival of 80-85%. The combined modality approach results in fewer relapses but overall survival is similar. In order to reduce the long term morbidity of radiation current trials are exploring combined modality treatment with lower radiation doses versus chemotherapy alone. 

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