Paclitaxel Cyclophosphamide

CYCLOPHOSPHAMIDE PACLITAXEL t risk of neutropenia, thrombocytopenia and mucositis when paditaxel is infused over 24 or 72 hours prior to cyclophosphamide Mechanism is uncertain Administer cyclophosphamide first and then follow with paditaxel... 

Cyclophosphamide 600 mg/m2 IV, day 1 Methotrexate 40 mg/m2 IV, day 1 Fluorouracil 600 mg/m2 IV, days 1 and 8 Repeat cycles every 28 days for 6 cycles Dose-dense AC —> paclitaxel Doxorubicin 60 mg/m2 IV bolus, day 1 Cyclophosphamide 600 mg/m2 IV, day 1 Repeat cycles every 14 days for 4 cycles (must be given with growth factor support) Followed by ... 

AC, Adriamycin (doxorubicin), Cytoxan (cyclophosphamide) CAF, Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), 5-fluorouracil CEF, cyclophosphamide, epirubicin, 5-fluorouracil CMF, cyclophosphamide, methotrexate, 5-flourouracil FAC, 5-fluorouracil, Adriamycin (doxorubicin), cyclophosphamide FEC, 5-fluorouracil, epirubicin, cyclophosphamide TAC, Taxol (paclitaxel), Adriamycin (doxorubicin), cyclophosphamide. 

Some lymphomas, for example, are related to overexpression of Bcl-2. Antisense oligonucleotides are specially designed to target the overexpression of Bcl-2. Oblimersen (Genasense) is an antisense drug by Genta to block Bcl-2 production and enhance the efficacy of other standard chemotherapy drugs such as paclitaxel, fludarabine, irinotecan, and cyclophosphamide. 

Piccart MJ, Bertelsen K, James K, et al. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer three-year results. J Natl Cancer Inst 2000 92(9) 699-708. 

Trastuzumab (Herceptin) [Antineeplastic/Monoover express the HERlIneu. protein breast CA adjuvant, w/ doxorubicin, cyclophosphamide, and paclitaxel if pt HER2/neu(+) Action MoAb binds human EGF receptor 2 protein HER2) mediates cellular cytotox Dose Per protocol, typical 2 mg/kg/IV/wk Caution [B, ] CV dysfxn, alla-gy/inf Rxns Contra Live vaccines Disp Inj SE Anemia, cardiomyopathy, nephrotic synd, pneumonitis Interactions t Risk of cardiac dysfxn W/ anthracycline, cyclophosphamide, doxorubicin, epirubicin EMS Cardiomyopathy, ventricular dysfxn and pulm tox have been reported monitor for Sxs of reduced cardiac Fxn OD Sxs unknown... 

Chemotherapy Cyclophosphamide, erlotlnlb, ifos-famide, paclitaxel, tamoxifen, vinblastine, vincristine HIV protease inhibitors Amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir HMG-CoA reductase inhibitors Atorvastatin, lovastatin, simvastatin... 

McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY et al. Cyclophosphamide and cis-platin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl JMed 1996 334 1-6. 

Most anticancer drugs damage hair follicles and produce partial or complete alopecia. Patients should be warned of this reaction, especially if paclitaxel, cyclophosphamide, doxorubicin, vincristine, methotrexate, or dactinomycin is used. Hair usually regrows normally after completion of chemotherapy. 

Herceptin with cisplatin, doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel. A comparison of serum levels of trastuzumab given in combination with various chemotherapeutic agents did not suggest the possibility of any pharmacokinetic interactions except in combination with paclitaxel. Although not statistically signihcant, mean serum trough concentrations of trastuzumab were consistently elevated, about 1.5-fold, when Herceptin was administered in combination with paclitaxel. However, trastuzumab and paclitaxel were used concurrently in clinical trials with positive outcome results. The concurrent administration of anthracyclines, cyclophosphamide, and trastuzumab increased the incidence and severity of cardiac dysfunction during clinical trials. 

Patient HER2 Levels" Herceptin Paclitaxel Paclitaxel and Herceptin AnthracycUne + Cyclophosphamide Anthracycline + Cyclophosphamide and Herceptin... 

Carcinoma of breast (1) Adjuvant chemotherapy or tamoxifen after primary breast surgery Cyclophosphamide, doxorubicin, vincristine, methotrexate, fluorouracil, paclitaxel, mitoxantrone, prednisone, megestrol, androgens,1 aminoglutethimide, trastuzumab... 

Carcinoma of ovary Cisplatin or carboplatin plus paclitaxel Cyclophosphamide, doxorubicin, melphalan, fluorouracil, vincristine, altretamine, bleomycin... 

Combination chemotherapy is the standard approach to stage III and stage IV disease. Randomized clinical studies have shown that the combination of paclitaxel and cisplatin provides survival benefit compared with the previous standard combination of cisplatin plus cyclophosphamide. More recently, several studies have shown that carboplatin and paclitaxel yields clinical results similar to what is achieved with the cisplatin plus paclitaxel combination however, because of reduced toxicity and greater ease of administration, carboplatin plus paclitaxel has now become the treatment of choice. In patients who present with recurrent disease, the topoisomerase I inhibitor topotecan, the alkylating agent altretamine, and liposomal doxorubicin are used as single agent monotherapy. 

All patients had stage IV breast cancer receiving first-line chemotherapy, either AC (doxorubicin or epirubicin plus cyclophosphamide) or T (paclitaxel). Data from Slamon et al. (250). 

Ayers M, Symmans WF, Stec J, Damokosh Al, Clark E, Hess K, et al. Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouraril, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 2004 22(12)2284-2293. 

Reynolds T, Baughman S, Schofield C, Palazzolo M, Dalgard D, Thomas DA. A 3-week interaction study of rhuMAb HER2 with doxorubicin, cyclophosphamide and paclitaxel in rhesus monkeys. Toxicologist 1996 30(1) 36. 

Fig. 3 Venn-diagram for selected compounds interacting with the key MDR-related ABC transporters. MDR-substrate anticancer agents. Abbreviations VCR vincristine, VP-16 etoposide, STER steroids, TAM tamoxiphen, TKI-INHIB tyrosin kinase inhibitors e.g. STI-571, DOX doxorubicine or adriamycin, DNR daunorubicin, EPIR epirubicin, MX mitoxantrone, TOPOT topotecan, iridotecan, BISANT bisanthrone, COLCH colchicin, ACT-D actinomycin D, MYTOM mytomycin, TX methotrexate, CPHAM cyclophosphamide, CHLB chlorambucil, CARM carmustine, LCV leucovorin, HUR hydroxy urea, CISPL cisplatin, TAXOL paclitaxel. (Reproduced from [4])...

Squalamine has been tested in mammary, ovary, and lung cancer xenograft mouse models [20,23-26]. Results sho ved that squalamine alone had a modest effect on tumor growth delay and in some cases it resulted in decreased number of lung metastases. However, in most studies, squalamine treatment was more efficacious when combined with previously established anticancer agents such as cyclophosphamide, cisplatin, carboplatin, paclitaxel, 5-fluorouracil, or genestein, or with radiation therapy. 

TRASTUZUMAB CYCLOPHOSPHAMIDE, DAUNORUBICIN, IDARUBICIN, PACLITAXEL t risk of cardiac toxicity Possibly additive cardiac toxic effect Monitor cardiac function closely-clinically and electrocardiographically. Avoid co-administration of trastuzumab with idarubicin except in clinical trials... 

The incidence of neutropenia has also been investigated in combination schedules. Patients receiving paclitaxel in combination with cyclophosphamide have severe neutropenia more often than with single treatment (72% of patients). Paclitaxel given as a 24-hour infusion before cyclophosphamide is more likely to cause severe neutropenia compared with patients who receive cyclophosphamide first (31). 

Cardiotoxicity is a major concern with trastuzumab, particularly as it is often used in patients who are receiving or who have previously received anthracychne antibiotics (2). It occurs in 5% of patients given trastuzumab alone, in 13% of patients given trastuzumab with paclitaxel, and in 27% of patients given trastuzumab in combination with anthracyclines and cyclophosphamide (3). 

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