Combination therapy approach

The possibilities for a prohealing approach using 173-estradiol remains of clinical relevance either as monotherapy or as adjunctive therapy. The combination therapy approach could be an effective way to decrease the dose or potential negative effects of a given antiproliferative compound and combine the beneficial effects of l7(3-estradiol to optimize vascular healing. 

A crucial issue for antiviral therapy is the fact that all antiviral substances rapidly select for resistance thus, monitoring and overcoming resistance has become a most important clinical paradigm of antiviral therapy. This calls for cautious use of antiviral drugs and implementation of combination therapies. In parallel, efforts in drug discovery have to be continued to develop compounds with novel mode-of-action and activity against resistant strains. This book reviews the current status of antiviral therapy, from the roads to development of new compounds to their clinical use and cost effectiveness. Individual chapters address in more detail all available drug classes and outline new approaches currently under development. 

A variety of pharmacologic approaches are available and may be prescribed as single or combination therapy for prophylaxis of PONV. See Table 27-8 for doses of specific agents. 

Venturelli, S., Armeanu, S., Pathil, A., Hsieh, C.J., Weiss, T.S., Vonthein, R., Wehrmann, M., Gregor, M., Lauer, U.M. and Bitzer, M. (2007) Epigenetic combination therapy as a tumor-selective treatment approach for hepatocellular carcinoma. Cancer, 109, 2132-2141. 

Socinski et al. have reported on their phase I/II experience with dose-escalated thoracic radiation in the setting of a combined modality approach to locally advanced NSCLC (55,64). Two cycles of carboplatin and paclitaxel (AUC 6 and 225 mg/m2/3h q21d) were followed on d 43 by weekly carboplatin and paclitaxel (AUC 2 and 45 mg/ m2/3h x 6) and thoracic radiotherapy (TRT), 50 Gy was delivered to the prechemotherapy tumor volume and areas of suspected microscopic spread in the mediastinum with a 1.0-2.0 cm margin. Boost volumes included the primary tumor volume and all radiographically positive nodes with a 1.0 cm margin. The total dose of radiation was escalated through four cohorts of patients 60,66,70,74 Gy without reaching any of the planned toxicity endpoints. The overall response to the therapy was 50% (3% CR, 47%... 

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. 

Targeting is an excellent concept, however, its efficiency is not always satisfactory. Other approaches are being used such as the use of photosensitizers in polymer-anticancer drug conjugates which permits double targeting and combination therapy. 

Because significant OCD symptoms often remain or recur, even when there is substantial improvement with a specific therapy, a combined complementary approach seems to be the optimal strategy for most patients. 

Another approach to the management of IM resistance is to combine agents that are individually active against CML but have differing mechanisms of action that may allow either additive or synergistic effects in a non-cross-resistant marmer. This approach has been extensively studied in the literature and will not be reviewed in detail here. An excellent discussion of combination therapy is foimd in the reviews by Hochhaus and La Rosee (52,85). Some combination approaches have utilized famesyl transferase inhibition such as lonafamib in combination with IM, inhibitors of the mammalian target of rapamycin (mTOR) in combination with IM and combining mycophenolic acid, an inhibitor of the JAK-STAT pathway. 

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