TC Arm Research Articles

Clinical study of combined chemotherapy of domestic paclitaxel and vinorelbine plus platinum for advanced non-small cell lung cancer

To evaluate the efficacy and toxicity of combined chemotherapy of domestic paclitaxel and vinorelbine plus cisplatin and carboplatin in the treatment of advanced non-small cell lung cancer (NSCLC). A total of 181 initially treated patients with advanced NSCLC were enrolled in this study and treated by NP (vinorelbine plus cisplatin), TC (domestic paclitaxel plus carboplatin) and TP (domestic paclitaxel plus cisplatin). The efficacy and side effects were analysed after at least two cycles of chemotherapy. The overall response rates (CR+PR) were 42.4% in the NP arm, 40.3% in the TC arm and 43.3% in the TP arm respectively. No significant statistical difference was found among the three groups ( Chi-square= 0.108 6 , P > 0.05). The median survival times were 8.4 months, 9.4 months and 8.9 months respectively in the NP, TC and TP groups ( P > 0.05). The 1-, 2-, 3-year survival rates were 39.0%, 16.9%, 5.1% in the NP group and 41.9%, 21.0%, 6.5% in the TC group and 40.0%, 18.3%, 5.0% in the TP group respectively. No significant statistical difference was found among the three groups ( Chi-square=0.140 4, P > 0.05). The major side effects were myelosuppression, alopecia and nausea/vomiting in the three groups. There were no chemotherapy-related death among the three groups. The combined regimens of NP, TC and TP are effective and well-tolerated regimens for advanced NSCLC.

First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin

The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.

First-line treatment of ovarian cancer FIGO stages IIb–IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin

The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease &lt;1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis ≥ grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P= 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.

Combined Analysis of Two-Year Follow-Up from Two Open-Label Randomized Trials Comparing Efficacy of Three Nucleoside Reverse Transcriptase Inhibitor Backbones for Previously Untreated HIV-1 Infection: OzCombo 1 and 2

Purpose: To compare inhibition of HIV replication, improvements in CD4+ T-cell counts, metabolic parameters, and body shape changes after 2 years of assigned therapy in OzCombo patients. Method: Study participants were those who were recruited into the open-label OzCombo 1 (1996/1997) and OzCombo 2 (1997/1998) trials. Patients in OzCombo 1 were randomized to receive indinavir in combination with zidovudine+lamivudine (AZT+3TC; n = 35), stavudine (d4T)+3TC (n = 34), or d4T+didanosine (ddI) (n = 37). OzCombo 2 patients were randomized to the same nucleoside reverse transcriptase inhibitor (NRTI) backbones with nevirapine (n = 20, 22, 23, respectively). The mean time-weighted changes from baseline in CD4 T-cell count/mL, HIV RNA (log copies/mL plasma), and proportions with detectable viral load (<500 copies plasma HIV RNA/mL) between NRTI arms over 2 years were compared by formal meta-analysis. A cross-sectional study of metabolic and body shape complications was also undertaken. Results: For the comparison of d4T+3TC and d4T+ddI to AZT+3TC, mean differences in time-weighted change from baseline in CD4 T-cell count/μL and log copies HIV RNA/mL adjusted for baseline CD4+ T-cell and HIV RNA counts were: –44 (p = .08) and –14 (p = .56) cells/μL and –0.1 (p = .40) and –0.1 (p = .6) copies/mL. Odds ratios for detectable viral load in the last study quarter were 0.6 (p = .44) and 1.0 (p = .95). The mean percent leg fat was lower in the d4T+3TC and d4T+ddI than the AZT+3TC arm (mean difference 5.1% [p = .07] and 7.6% [p = .02], respectively). Conclusion: For all regimens, virological control and immunological response were maintained over 2 years. Regimens containing d4T and particularly d4T+ddI were significantly associated with increased peripheral fat loss compared with AZT+3TC.

Combined Analysis of Two-Year Follow-Up from Two Open-Label Randomized Trials Comparing Efficacy of Three Nucleoside Reverse Transcriptase Inhibitor Backbones for Previously Untreated HIV-1 Infection: OzCombo 1 and 2

Purpose: To compare inhibition of HIV replication, improvements in CD4+ T-cell counts, metabolic parameters, and body shape changes after 2 years of assigned therapy in OzCombo patients. Method: Study participants were those who were recruited into the open-label OzCombo 1 (1996/1997) and OzCombo 2 (1997/1998) trials. Patients in OzCombo 1 were randomized to receive indinavir in combination with zidovudine+lamivudine (AZT+3TC; n = 35), stavudine (d4T)+3TC (n = 34), or d4T+didanosine (ddI) (n = 37). OzCombo 2 patients were randomized to the same nucleoside reverse transcriptase inhibitor (NRTI) backbones with nevirapine (n = 20, 22, 23, respectively). The mean time-weighted changes from baseline in CD4 T-cell count/mL, HIV RNA (log copies/mL plasma), and proportions with detectable viral load (<500 copies plasma HIV RNA/mL) between NRTI arms over 2 years were compared by formal meta-analysis. A cross-sectional study of metabolic and body shape complications was also undertaken. Results: For the comparison of d4T+3TC and d4T+ddI to AZT+3TC, mean differences in time-weighted change from baseline in CD4 T-cell count/μL and log copies HIV RNA/mL adjusted for baseline CD4+ T-cell and HIV RNA counts were: –44 (p = .08) and –14 (p = .56) cells/μL and –0.1 (p = .40) and –0.1 (p = .6) copies/mL. Odds ratios for detectable viral load in the last study quarter were 0.6 (p = .44) and 1.0 (p = .95). The mean percent leg fat was lower in the d4T+3TC and d4T+ddI than the AZT+3TC arm (mean difference 5.1% [p = .07] and 7.6% [p = .02], respectively). Conclusion: For all regimens, virological control and immunological response were maintained over 2 years. Regimens containing d4T and particularly d4T+ddI were significantly associated with increased peripheral fat loss compared with AZT+3TC.

Evolution of Antiretroviral Phenotypic and Genotypic Drug Resistance in Antiretroviral-Naive HIV-1-Infected Children Treated with Abacavir/Lamivudine, Zidovudine/Lamivudine or Abacavir/Zidovudine, with or without Nelfinavir (The Penta 5 Trial)

To describe the evolution of resistance to zidovudine (ZDV), lamivudine (3TC), abacavir (ABC) and nelfinavir (NFV), 113 previously untreated children in the PENTA 5 trial had resistance assayed at baseline, rebound and/or 24, 48, 72 weeks (VIRCO: phenotyping and genotyping with 'Virtual Phenotype' interpretation). At baseline, few reverse transcriptase mutations and no primary protease inhibitor mutations were observed. Time to detectable HIV-1 RNA with reduced phenotypic susceptibility to any drug was shortest in the ZDV+3TC arm (overall logrank P=0.02). Through a median follow-up of 55 weeks, at their last assessment 11 (28%), 16 (40%) and 13 (32%) children with detectable HIV-1 RNA and a resistance test available had mutations conferring resistance to none, one, or two or more trial drugs, respectively, according to the virtual phenotype. Reduced phenotypic susceptibility to ABC only occurred in the 3TC+ABC arm and required K65R and/or L74V in addition to M184V. NFV-resistant virus was selected slowly through D30N or L90M pathways, and selection of ZDV-resistant virus was rare. Selection of 3TC-resistant virus was most frequent, followed by NFV and/or ABC; selection of ZDV-resistant virus was rare. Importantly, although in vitro, ABC selects for M184V as the first mutation, ABC did not select for M184V when combined with ZDV without 3TC. The most sustained HIV-1 RNA response was in the 3TC+ABC arm, but mutations conferring reduced susceptibility to 3TC and/or ABC evolved more frequently if virological failure occurred with 3TC+ABC than with ZDV+ABC.

Randomized Trial of Opioids Versus Tricyclic Antidepressants for Radiation-Induced Mucositis Pain in Head and Neck Cancer

Patients who receive radiotherapy for head and neck cancer are likely to develop painful mucositis. The pain is characterized by a burning or stinging sensation similar to neuropathic pain sensations. The purpose of the present study was to compare the analgesic effect of a tricyclic antidepressant (TC), commonly used in the treatment of neuropathic pain, with the effect of opioids on radiation-induced mucositis pain. Forty-three patients receiving 66–68 Gy external radiation according to the DAHANCA guidelines (the Danish Head and Neck Cancer Study Group) were randomized to either morphine or TC when mucositis pain was insufficiently managed with weak analgesics. Patients with insufficient pain control in either treatment arm received supplementary medication from the opposite treatment arm. Pain was evaluated weekly using a VAS scale and the McGill Pain Questionnaire. The degree of mucositis and the degree of depression were measured at the same time intervals. Twenty-two patients entered the opioid arm and 21 the TC arm. Two patients in each arm were non-evaluable. VAS pain scores were significantly reduced in the opioid treatment arm one week after randomization (p=0.01). Eight patients in the TC arm were managed with TC alone, but for 11 patients it was necessary to add morphine. The 20 evaluable patients in the morphine arm required no additional treatment. There were no significant differences in side effects between the two groups. Higher pain scores in the TC arm, but not in the opioid arm, were significantly correlated with higher BDI scores. Some head and neck cancer patients with radiation-induced nucositis pain may have sufficient pain control on TC alone. This might be useful in patients with relative counter-indications to opioid treatment.