Paclitaxel Doxorubicin

Since the discovery of vesicular structures, termed liposomes, by Alec Bangham, a tremendous amount of work on applications of liposomes has emerged. The use of small unilamellar liposomes as carriers of drugs for therapeutic applications has become one of the major fields in liposome research. The majority of these applications are based on the encapsulation of water-soluble molecules within the trapped volume of the liposomes. Long circulating poly(ethylene glycol) (PEG) modified liposomes with cytotoxic drugs doxorubicin, paclitaxel, vincristine, and lurtotecan are examples of clinically applied chemotherapeutic liposome formulations (1,2). 

Advani R, Fisher GA, Lum BL, et al. A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC833), a modulator of multidrug resistance. Clin Cancer Res 2001 7 1221-1229. 

DOXORUBICIN PACLITAXEL t risk of neutropenia, stomatitis and cardiomyopathy due to t plasma concentrations of doxorubicin t risk of neutropenia, stomatitis and cardiomyopathy due to t plasma concentrations of doxorubicin when paditaxel is given before doxorubicin Doxorubicin should be administered prior to paditaxel. The cumulative dose of doxorubicin should be limited to 360 mg/m2 when concurrently administered with paditaxel... 

Advani R, Lum BL, Fisher GA, Halsey J, Chin DL, Jacobs CD, Sikic BI. A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (psc-833), an inhibitor of multidmg resistance. Ann Oncol 2005 16 1968-1973. 

Chitosan nanoparticles have also been formulated and evaluated for their anti-cancer potential. It has been reported that the smaller the particle size and higher the positive surface charge, the better its anti-cancer activity is. It showcases its action mainly by disruption of the membrane and induction of apoptosis [44]. The immunostimulatory potential of chitosan is also believed to be one of the factors alleviating its anti-cancer activity [45]. Chitosan nanoparticles have also been used as a drug carrier for delivery of anti-cancer drugs such as doxorubicin, paclitaxel, docetaxel and norcantharidin [46]. 

Polymeric micelles Synthetic Controlled and sustained drug delivery Doxorubicin, Paclitaxel... 

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 ... 

Paclitaxel also may be given concurrently with doxorubicin or epirubicin as a combination regimen. Pharmacokinetic interactions make these regimens more difficult to give. 

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. 

Baselge, ]., et al., "Recombinant Humanized Anti-HER2 Antibody (HERCEPTIN) Enhances the Antitumor Activity of Paclitaxel and Doxorubicin Against HER2/neu Overexpressing Human Breast Cancer Xenografts," Cancer Res., 58, 2825-2831 (1998). 

Chemotherapeutic agents that have significant cancer response when combined with hyperthermia (up to 43°C) include doxorubicin, melphalan, mitomycin C (MMC), mitoxantrone, gemcitabine, etoposide, and especially the platinum-based agents carboplatin and oxaliplatin (Mohamed et al., 2003 Sugarbaker et al., 2005). Agents that do not work well with hyperthermia include irinotecan, paclitaxel, docetaxel, 5-fluorouracil, and floxuridine (Mohamed et al., 2003 Sugarbaker et al., 2005). 

Gordon AN, Granai CO, Rose PG, et al. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol 2000 18 3093. 

Anticancer drugs Paclitaxel Docetaxel Vinblastine Vincristine Tipifarnib Diflomotecan Iiinotecan Doxorubicin Daunorubicin Etoposide Tenoposide Tamoxifen (i)... 

Anticancer drugs Methotrexate Doxorubicin Daunorubicin Epirubicin Etoposide Vincristine Vinblastine Paclitaxel Iiinotecan... 

Formenti, 2001 (34) 44 Concurrent paclitaxel/RT/surgery/post-op Doxorubicin-based CT 35% NA NA... 

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... 

Miglietta A. et al., Cellular uptake and cytotoxicity of solid lipid nanospheres (SEN) incorporation doxorubicin or paclitaxel, Int. J. Pham., 210, 61, 2000. 

Fleming GF, Brunetto VL, Celia D, Look KY, Reid GC, Munkarah AR et al. Phase III study of doxorubicin plus cisplatin with or without paclitaxel plus filgastrim in advanced endometrial carcinoma a Gynecologic Oncology Group study. J Clin Oncol 2004 22 2159-66. 

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. 

Paclitaxel is among the most active of all anticancer drugs, with significant efficacy against carcinomas of the breast, ovary, lung, head, and neck. It is combined with cisplatin in the therapy of ovarian and lung carcinomas and with doxorubicin in treating breast cancer. 

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. 

Investigators found that human breast cancer cell lines with BRCAl mutations showed a twofold to fourfold increase in apoptosis after treatment with ionizing radiation, cisplatin, or doxorubicin, compared with cells free of mutations. They also found that BRCAl tumor cell lines were resistant to other agents, such as paclitaxel (Taxol) and docetaxel (Taxotere), treatments used commonly in ovarian cancer and advanced-stage breast cancers. 

Neopharm LED doxorubicin Inex onco TCS vincristine Neopharm LEP paclitaxel Elan inyocet doxorubicin Gilead ambisome amphoteracin Gilead daunXome daunorubicin Alza doxil doxorubicin QLT visudyn verteporfin... 

Block copolymer micelle formulations of doxorubicin and paclitaxel are both in Phase l/ll trials for the treatment of advanced cancers. Aliabadi and Lavasanifar (2006) recently compiled a review of the clinical status of polymeric micelle systems for anticancer agent delivery. 

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