Double-drug Regimens Research Articles

Effect of platinum based dual drug second-line therapy on prognosis of NSCLC patients and relative factors analysis

Objective To analyze the prognostic implications of second-line double drug regimens for advanced non-small cell lung cancer (NSCLC) patients and related factors. Methods Eighty patients with advanced NSCLC who were accepted from January 2014 to December 2016 in our hospital were chosen as the research objects. The patients were randomly divided into two groups using the random number table method, namely single drug group (n=40) and double drug group (n=40). The patients in single drug group were treated with docetaxel or pemetrexed, and the patients in double drug group were treated with docetaxel, pemetrexed, vinorelbine or paclitaxel combined with platinum (cisplatin). The effects of patients in the two groups were compared and the factors affecting the prognosis of the patients were analyzed. Results The remission rate in the double drug group was significantly higher than that in the single drug group (45.0% vs. 20.0%; χ2=4.493, P=0.021). The results of single factor analysis for patients in double drug group showed that pathological type (χ2=7.511, P=0.023), time from first-line treatment to second-line treatment (χ2=6.412, P=0.041), second-line baseline TNM stage (χ2=4.022, P=0.045), second-line cycle number (χ2=5.065, P=0.027), leukopenia (χ2=4.852, P=0.033) and neuron specific enolase (χ2=9.243, P=0.002) were the main prognostic factors of the second-line chemotherapy. The results of multivariate analysis for patients in double drug group showed that time from first-line treatment to second-line treatment (OR=3.511, 95%CI: 1.486-3.602, P=0.033), second-line baseline TNM stage (OR=1.623, 95%CI: 1.127-2.119, P=0.027), second-line cycle number (OR=2.208, 95%CI: 1.589-2.827, P=0.014) and neuron specific enolase (OR=1.960, 95%CI: 1.209-2.773, P=0.025) were independent prognostic factors. Conclusion The remission effect of double second-line treatment scheme based on platinum for patients with NSCLC is good, and the time form first-line treatment to second-line treatment, second-line baseline TNM stage, second-line cycle number and neuron specific enolase are independent prognostic factors. Key words: Carcinoma, non-small-cell lung; Drug therapy; Platinum compounds; Antineoplastic combined chemotherapy protocols; Influencing factors

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Adjuvant intravesical therapy based on an in vitro cytotoxicity assay in the management of superficial transitional cell cancer of the urinary bladder

To investigate the utility of an individualized chemo/immunotherapy regimen of intravesical therapy based on the results of an assessment of in vitro cytotoxicity. Intravesical adjuvant chemo/immunotherapy was given to 47 patients based on the results of in vitro cytotoxicity assay of the responses of cultured autologous tumour cells to various cytotoxic drugs (mitomycin-C, doxorubicin and cisplatin) and immunomodulating agents (bacillus Calmette-Guérin, BCG and interferon-alpha2b). Intravesical therapy was given as single- or double-drug regimens according to the assay results: 16 (34%) patients showed cytotoxicity to a single drug and 31 (66%) showed maximum cytotoxicity to a combination of immunomodulators and cytotoxic agents. The efficacy of treatment in terms of tumour-free survival and recurrence rate was compared with 40 patients receiving intravesical BCG according to International Protocol (control group). In the in vitro assay group, seven patients (15%) had tumour recurrence, compared to 15 (38%) in the control group (P = 0.02). In the in vitro group, one of 16 patients on a single drug and six on the double-drug regimen had a recurrence. The patients given BCG with cytotoxic drugs had no recurrences, but 29% of patients given interferon-alpha2b combinations had recurrences. Kaplan-Meier analysis showed a longer recurrence-free survival in the in vitro group (75%) than in the control group (49%) at 48 months of follow-up. Intravesical therapy based on an in vitro cytotoxicity assay is an attempt to give individualized therapy, and to increase tumour-free survival in these patients, with no side-effects. Recurrences in seven patients in the in vitro group might be due to a defective host immune response, or to expansion of a subclone of tumour cells resistant to all treatment.

Evaluation of a triple-drug combination for treatment of experimental multidrug-resistant pneumococcal meningitis

To evaluate the therapeutic efficacy of ceftriaxone+vancomycin+rifampicin (CVR) in the treatment of pneumococcal meningitis caused by a multidrug-resistant strain, single-drug regimens (ceftriaxone 100 mg/kg, rifampicin 15 mg/kg, or vancomycin 20 mg/kg), double-drug regimens (ceftriaxone+vancomycin [CV] and ceftriaxone+rifampicin [CR]) and a triple-drug combination (CVR) with or without dexamethasone were compared in a rabbit meningitis model. Meningitis was induced by a highly penicillin-resistant (MIC 2 mg/l) and ceftriaxone-resistant (MIC 4 mg/l) pneumococcal strain. Final therapeutic efficacy was evaluated by the bacterial concentration at 24 h, and the bacterial killing rate was also evaluated. All combination regimens were superior to ceftriaxone or vancomycin single-drug regimens with regard to sterilisation of CSF and bacterial killing rate. Rifampicin was as effective as combination regimens. Regardless of dexamethasone, therapeutic efficacy of CVR and CR were superior to that of CV. CVR showed comparable therapeutic efficacy to CR. Data suggested that CVR would not have additional therapeutic benefit over CR during the initial 24 h of treatment.

Treatment Choices for Second-Line Chemotherapy of Metastatic Breast Cancer

A vast array of new cytotoxic drugs has opened the possibility for second- and third-line treatment of patients with metastatic breast cancer pretreated by anthracyclines and/or taxanes. These new drugs include capecitabine, gemcitabine, liposomal doxorubicin, vinorelbine and even some of the older agents administered in weekly schedules. These drugs can be administered as either monotherapy or polychemotherapy mainly consisting of double-drug regimens. Phase II studies of these drugs have produced such favorable data that patients with metastatic breast cancer pretreated with anthracyclines and/or taxanes can safely be offered either of these agents and phase III studies are definitely warranted in this patient population. Currently, data from one phase III trial are available in which docetaxel plus capecitabine was found to result in significantly prolonged time to disease progression and overall survival as compared to docetaxel alone in anthracycline-pretreated patients with advanced breast cancer. No golden standard has emerged, however, for patients pretreated with taxanes and anthracyclines further underlining the need of testing various cytotoxic compounds either as monotherapy or in combination with other cytotoxic drugs in this setting.

Combination therapy with zidovudine, didanosine and saquinavir

The goal of AIDS Clinical Trials Group (ACTG) Protocol 229 was to evaluate the shorter term (24 week) and longer term (48 week) safety and activity of the HIV-1 proteinase inhibitor saquinavir in combination with zalcitabine (ddC) and zidovudine (ZDV) versus saquinavir in combination with ZDV versus ddC in combination with ZDV. This study confirms and extends the conclusions from the first 24 weeks of this study and showed that in subjects with extensive prior antiretroviral experience, the triple combination of saquinavir, ddC and ZDV was well-tolerated, safe and remained superior to the other double drug regimens as measured by CD4 + cell counts, quantitative HIV-1 microculture and plasma HIV-1 RNA levels.

Renal allograft immunosuppression III. Triple therapy versus three different combinations of double drug treatment: two year results in kidney transplant patients

Abstract. A prospective randomized trial was carried out to compare the long-term effects of triple therapy based on low-dose cyclosporin A (CyA), low-dose methylprednisolone (MP) and azathioprine (Aza) with three different double drug immunosuppressive regimens. After initial triple drug immunosuppression for 10 weeks, 128 patients were randomized into four different immunosuppressive groups: one group continued with triple therapy (group A) and the three other groups were treated with different combinations of two drugs: Aza and CyA (group B), Aza and MP (group C) and CyA and MP (group D). This report presents the 2-year results. For groups A, B, C and D, graft survivals were 75%, 78%, 84% and 81%, respectively, and patient survivals were 84%, 84%, 84% and 94%, respectively. After 2 years no patient had returned to dialysis in group C compared with one to three patients in every CyA-using group. However, at the end of the 2nd year, group C included more patients with deteriorating graft function than the other groups. Median serum creatinine was 107, 120,139 and 129 μmol/l for groups A, B, C and D, respectively. For the patients who remained on the original randomized protocol, there were no significant differences in graft function tests between the four groups, the median creatinine being 115,115,118 and 113 μmol/l for groups A, B, C and D, respectively. Thus, no graft deterioration had occurred during the 2 years for these patients following the original protocol. Our results suggest that after initial triple therapy, patients with a first cadaveric kidney allograft can either continue with triple therapy orbe converted toany of the double drug regimens without detriment to graft function, graft survival or patient survival for the next 2 years. This will allow more flexible and individual immunosuppressive treatment.

Renal allograft immunosuppression: II. A randomized trial of withdrawal of one drug in triple drug immunosuppression

Abstract. A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidney allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n= 12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81 %, 88%, 88%, and 88%, respectively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 μmol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3. 5–4. 2 mg/kg per day and CyA concentrations were equal.