| Statistics indicate that the inc idence of lung cancer is the leading cancer site in males, comprising 17% of the total new cancer and 23% of the total cancer deaths in developing countries. The mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. There were 1.6 million of the total new lung cases in 2008. Moreover, the clinical diagnosis of many Chinese patients occurs when these individuals have late-stage cancer and therefore no longer have the opportunity to receive radical surgical treatment. Chemotherapy has become an important method of cancer treatment, however, most patients undergo either relapse or metastasis following first-line chemotherapy, requiring second-line and subsequent treatments. The National Comprehensive Cancer Network guidelines recommend docetaxel alone and pemetrexed alone as the standard second-line chemotherapy regimens of NSCLC. But treatment efficiency in second-line treatment of NSCLC is unsatisfactory. The total effective rate is 29.7%, median survival time is 7.9-8.3 months, and 1-year overall survival rate is only 29.7%. So, it has important clinical s ignificance to explore the efficacy of combination chemotherapy regimen in previously treated patients with NSCLC.Cisplatin(DDP)-based chemotherapy is significant in cancer treatment, however, due to its toxicity, particularly nephro- and neuro-toxicity, DDP-based chemotherapy has limited applications. Therefore, researchers have pursued a new platinum compound. Lobaplatin(LBP), which is a class III platinum anticancer drug developed by the German firm ASTA Medica(Degussa), is primarily used for the treatment of advanced breast cancer, small cell lung cancer(SCLC), and chronic myeloid leukaemia. Research has demonstrated that LBP has various advantageous properties, inc luding strong anticancer activity, no significant nephrotoxicity or neurotoxic ity, no requirement for hydration/liquid infus ion, a much lower incidence of drug resistance than DDP, and no cross-resistance with DDP. A number of studies have revealed that LBP has broad-spectrum anticancer activity, including efficacy against lung cancer, breast cancer, colorectal cancer, testicular cancer, and lymphoma.Docetaxel(TXT) is a semisynthetic compound in the taxane class of anti-cancer drugs. It binds to free tubulin, promotes the assembly of tubulin into stable microtubules, and inhibits microtubule depolymerisation. These effects significantly decrease the quantities of free tubulin and thereby inhibit cell mitosis and proliferation. Single-agent chemotherapy with TXT is an important treatment approach for a variety of tumours. Studies have demonstrated that the administration of LBP in combination with TXT can produce certain therapeutic effects in patients with tumour progression after chemotherapy and that in this combination, LBP and TXT produce synergistic effects. However, the optimal LBP dose in this combination regimen has not been established based on the findings from phase I/II clinical trials. In particular, although international studies have established a recommended LBP dose of 50 mg/m2 for single-agent chemotherapy, no phase I studies on the appropriate LBP dose in the aforementioned combination regimen for second-line or third-line chemotherapy have been reported. In Europe and the USA, the recommended dose of TXT for second-line therapy is 75~100 mg/m2, however, Asian studies have suggested that a TXT dose of 60 mg/m2 is more suitable for East Asian populations. Our previous studies have demonstrated that Eastern and Western populations have different tolerances for the same doses of chemotherapy, with tolerated doses in the combination regimens for Eastern populations that are equivalent to 70% to 80% of the corresponding doses for Western populations. Therefore, it is unc lear whether chemotherapy doses determined based on studies of Western populations can be applied to Chinese patients.In this study, the maximum tolerated dose(MTD) of lobaplatin(LBP) when it was combined with docetaxel(TXT) for the treatment of solid tumours that had progressed following chemotherapy was determined, and toxic ities to this regimen were evaluated. A modified Fibonacci method was used for the dose escalation of LBP. The patients received TXT(at a fixed dose of 60 mg/m2) on day one(d1) and LBP(at an initial tested dose of 30 mg/m2) on day two(d2) of a treatment cycle that was repeated every 21 days. Each dose group consisted of at least three cases. In the absence of dose-limiting toxic ity(DLT), we proceeded to the next dose group, with a dose increment of 5 mg/m2 between groups, until DLT occurred. The dose immediately below the dose that produced DLT was regarded as the MTD. The 17 patients examined in this study completed a total of 58 cycles of chemotherapy, and a total of three dose-escalation groups(LBP 30 mg/m2, LBP 35 mg/m2, and LBP 40 mg/m2) were established. The main adverse event that was observed was myelosuppression. DLT occurred in four patients, including three patients in the LBP 40 mg/m2 group and one patient in the LBP 35 mg/m2 group. In total, three out of the four patients in the LBP 40 mg/m2 group exhibited DLT. We determined that the treatment administered to the LBP 35 mg/m2 group represented the MTD.Thus, our phase I trial revealed that the MTD for the tested LBP combination regimen was LBP 35 mg/m2 and TXT 60 mg/m2. This regimen resulted in mild adverse reactions and favourable patient tolerance. Therefore, we recommend the use of these dosages in phase II clinical trials. |
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