Patients with Refractory Disease

Patients wim BN uiuesponsive to psychotherapy alone should likely receive a trial of autidepressaut medicatiou wim coutinued psychotherapy. Switching to a different psychomerapeutic modality may be considered at this juncture as well. 

Additional options for refractory disorders include the augmentation of antidepressant treatment with an opiate blocking agent such as naltrexone or consideration of partial or full hospitalization to provide a more structured environment for normalizing the aberrant eating behavior. 

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Tricyclic Antidepressants (TCAs). The TCAs, particularly imipramine (Tofranil), were also discovered soon after their introduction to be effective in the treatment of panic attacks. Imipramine, the best-studied TCA in the treatment of panic disorder, is most often helpful at daily doses of 150-250 mg, though it must be started at 10-25 mg, usually at bedtime, and gradually increased over 2-4 weeks. Although they are not as well studied, many clinicians prefer to use the secondary amine TCAs, desipramine (Norpramin) and nortriptyline (Pamelor), because they have milder side effects than imipramine. Clomipramine (Anafranil), though probably the TCA with the greatest side effect burden, is often said to be most effective in patients with refractory disease. 

The NCCN guidelines recommend retreatment with either paclitaxel or platinum, or the combination of paclitaxel and a platinum compound if disease recurs more than 6 months after the initial treatment with paclitaxel in combination with a platinum analog. Treatment options for patients with refractory disease or disease recurrence within 6 months after treatment include topotecan, altretamine, oral etopo-side, liposomal doxorubicin, gemcitabine, tamoxifen, referral for a clinical trial, or supportive care therapy. 

Rihova, Ulbrich and colleagues have reported preliminary chnical experiments in six patients with refractory disease (angiosarcoma, and breast carcinoma) [107,108]. HPMA coplymer-Gly-Phe-Leu-Gly-doxorubicin (or... 

The primary goal in the treatment of multiple myeloma is to decrease tumor burden and minimize complications associated with the disease. A watch and wait approach is an option for asymptomatic patients who have no lytic lesions in the bone. Once symptoms occur, treatment is required. Chemotherapy can be used to reduce tumor burden in patients with symptomatic disease, but increasingly, immunomodula-tors such as thalidomide and dexamethasone are initial therapy. Almost all patients will become refractory to initial treatment and will require the use of salvage therapies such as bortezomib. Autologous stem cell transplantation prolongs overall survival in patients who can tolerate high-dose chemotherapy and may be the treatment of choice for many patients. 

PPIs are also efficacious in patients refractory to H2RAs and are more cost effective than H2RAs in patients with severe disease. 

Encouraging results with MAb-drug conjugates were seen in a phase I study with a conjugate of calicheamicin yli and a humanized anti-CD33 MAb in patients with refractory or relapsed AML [131]. Results support further evaluation in a setting of newly diagnosed or minimal-residual disease. 

Biological DMARDs are indicated when autoimmune inflammatory diseases are refractory to therapy with single traditional DMARDs or with combinations of oral or IV traditional DMARDs. Improvements of ACR 20 and ASAS 20 in over 70% of patients with refractory RA and AS do not mean much to the patients in terms of pain relief, improvement of function and health-related quality of life. The present biological DMARDs combined with MTX still cannot fully address the problems of the majority of patients with DMARDs refractory chronic progressive autoimmune inflammatory diseases. Those who are refractory to MTX - - biological DMARDs respond well to SBC-5-IMNs in over 80% of cases. 

E. Therapeutic response Intravitreal Vitravene therapy is effective in delaying disease progression in AIDS patients with refractory or newly diagnosed CMV retinitis depending on the patient population, the median time to progression has ranged from 2 to 11 weeks. 

In addition, currently the investigation of patients with refractory hypertension associated with end-stage renal disease are continuing to confirm the efficacy and safety of renal denervation by Ardian Inc (NCT00664638) [61], Catheter-based renal denervation has been reported as an effective and safe, without serious adverse events, treatment to reduce blod pressure in 45 patients with resistant hypertension for 12 months in a multicenter trial [62, 63],... 

Erythromycin has antidysrhythmic properties similar to those of Class lA antidysrhythmic drugs, and causes an increase in atrial and ventricular refractory periods. This is only likely to be a problem in patients with heart disease or in those who are receiving drugs that delay ventricular repolarization (5). High-doses intravenously have caused ventricular fibrillation and torsade de pointes (6). Each episode of dysrhythmia, QT interval prolongation, and myocardial dysfunction occurred 1-1.5 hours after erythromycin infusion and resolved after withdrawal. 

Many patients with Hodgkin s lymphoma will be refractory to initial therapy or will have a recurrence following a complete remission. Response to salvage therapy depends on the extent and site of recurrence, previous therapy, and duration of initial remission. High-dose chemotherapy and autologous hematopoietic stem cell transplantation should be considered in patients with refractory or relapsed disease. 

An objective response rate of less than 10% is anticipated for IP cisplatin in patients who fail to demonstrate at least a partial response to initial systemic cisplatin." Thns IP cisplatin should not be nsed in cisplatin-refractory patients. In addition to platinnm sensitivity and tumor size, extent of tumor spread must also be considered. IP therapy is most beneficial when the tmnor is confined to the abdomen." "" IP therapy is unlikely to have an advantage in patients with bnlky disease because drug penetration into larger tnmor nodnles is limited. AdditionaUy, patients best suited for IP administration shonld have limited IP adhesions with free fluid distribution. 

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