Free combination therapy

Free combination therapy (or drug). A therapy consisting in combining two or more individual treatments but without physically incorporating them into one formulation so that, unlike a fixed combination, each constituent treatment could still, in principle, be given alone. 

Combination therapy may provide improvement in longterm disease-free survival. The combination of fludarabine, cyclophosphamide, and rituximab improves CR rates compared with fludarabine alone (70% versus 20%) but at the expense of increased infections.28,29 Combinations of fludarabine and alemtuzumab are also being investigated, with the hope of improving overall survival.21... 

Takeda et al. (64) performed a phase I/II study consisting of low-dose CDDP (6-10 mg/m2/d) and UFT (600 mg/d) combined with radiotherapy (50 Gy/25 fractions) as postoperative adjuvant therapy following curative resection for patients with nonsmallcell lung cancer (NSCLC). The combined therapy was well tolerated and resulted in a disease-free survival rate of 78% at 2 yr. Another study in a small number of patients with unresectable stage III nonsmall-cell lung cancer, UFT (400 mg/m2 on d 1-52) and CDDP (80 mg/m2 on d 8,29, and 50) were administered with radiation therapy (total dose of 60.8 Gy in 38 fractions on d 1-52). Among 17 evaluable patients, 94% (16 patients) achieved partial responses with median time to tumor progression of 30 wk, and the... 

According to this criterion, the combined therapy was superior to the other three treatments, and drug therapy alone was little different from the control conditions with free appointments. An... 

Duda et al. prospectively studied 70 patients in the PROMPT trial of UK and abciximab versus UK alone. The trial showed the combination therapy resulted in a decreased infusion time, improved amputation free survival, and improved open surgery free survival at 90 days (46). Interestingly, a post hoc economic analysis of the PROMPT trial found an economic benefit to combination therapy at 90 days based on endpoints of amputation free survival, survival without open surgery, lack of major amputation and lack of major complications. The extra cost of abciximab was more than offset by the decreased costs through improved patient outcomes (47). 

The efficacy and adverse effects of various alternative treatment regimens for carcinoma in situ of the bladder have been compared with those of instillation of BCG in 21 patients. All were treated initially with intravesicular instillations of Keyhole-Limpet Hemocyanin (first course 20 mg weekly for six weeks second course 20 mg monthly for 1 year or bimonthly for 2 subsequent years). Patients who did not respond to two courses were treated with regular instillations of BCG Connaught strain 120 mg. Eleven patients were free from tumor tissue after the first or second course of Keyhole-Limpet Hemocyanin. Ten patients had to have a cystectomy because of persistence or progression of carcinoma after hemocyanin or hemocyanin with subsequent BCG. However, instillations of BCG caused severe dysuria in 60% and fever in 40% of patients, whereas hemocyanin treatment had only minor adverse effects (28). Combined therapy with mitomycin C and BCG was more effective in 28 patients with carcinoma in situ of the bladder than mitomycin alone (29). Compared with... 

The Mayo/NCCTG trial compared postoperative XRT alone, postoperative XRT with concurrent fluorouracil plus semustine chemotherapy, and pre- and postirradiation chemotherapy in a similar population of 204 patients with rectal cancer. This was the first randomized trial in which one cycle of combination chemotherapy was given before and after XRT in addition to the administration of fluorouracil during XRT. The use of combined chemotherapy and XRT significantly affected local recurrence, relapse-free survival, and OS as compared to XRT alone. Patients receiving combined therapy experienced an overall relative reduction of recurrence of 34% at... 

Because approximately two-thirds of patients who undergo resection of hepatic metastases will have disease recurrence, adjuvant systemic and hepatic arterial infusion chemotherapy have been studied in an attempt to improve long-term outcomes. A randomized trial that compared 6 months of hepatic floxuridine and dexamethasone plus TV fluorouracil with leucovorin to TV fluorouracil with leucov-orin alone following resection of hepatic metastases in 156 patients showed improved 2-year DPS (86% vs. 72%) and hepatic recurrence-free survival at 2 years (90% vs. 60%) with the combined therapy. Many practitioners offer adjuvant chemotherapy to select patients following potentially curative hepatic resection, but further studies, especially those involving more active agents, are needed to determine an optimal treatment regimen. ... 

Bleomycin causes DNA strand breaks by producing toxic free radicals. It is often used in combination therapy for lymphomas, head and neck and testicular cancer because it produces little bone marrow toxicity. It does however cause dose-dependent pulmonary fibrosis, oral ulcers, fever and chills. 

A few elinieal trials have been undertaken looking at the use of laetic acid bacteria as adjunetive therapy in the treatment of various types of eaneer. The elinieal efficacy of heat-killed LC9018 (Lactobacillus) in eombination with radiation was evaluated in a randomized eontrolled trial on 61 patients with carcinoma of the uterine eervix of Stage IIB or 111 (Okawa et al., 1989). Supplementation with LC9018 enhaneed the therapeutic effect of irradiation and also protected the patients from leukopenia during radiotherapy. The combination therapy also prolonged survival and the relapse-free interval eompared with radiation alone. 

Ankle edema occurred in about 5% of patients treated with both rosiglitazone and pioglitazone in some cases, pulmonary edema can develop. Edema was more frequent in insulin combination therapy with either drug (about 15% compared with 5.4-7% with insulin alone). The reasons for fluid retention and peripheral edema with TZDs are multifactorial. The increase in plasma volume may result from a reduction in renal excretion of sodium and an increase in sodium and free water retention. TZDs may also interact synergistically with insulin to cause arterial vasodilatation, leading to sodium reabsorption and an increase in extracellular volume [61,62], In case reports, the edema has not been responsive to diuretics [63,64]. 

Today, the ongoing emergence of multidrug-resistant bacteria and many diseases mainly caused by free radicals are serious global problems. Thus, new antimicrobials and novel approaches to combat these problems are urgently needed. Combination therapy is a new approach that may be helpful in treating multidrug-resistant bacteria... 

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