Abstract Objective To observe vinorelbine plus nedaplatin treatment of advanced esophageal effectiveness and security. Methods whole group of 35 patients, including 22 males and 13 females; aged 39 to 77 years, with a median age of 53 years; 29 cases of squamous cell carcinoma, and adenocarcinoma in 6 cases; initial treatment in 8 cases, 27 cases of retreatment, the retreatment should be used in patients with one and more than one chemotherapy given after enrollment, vinorelbine injection 25mg/m2 0.9% sodium chloride injection 100ml, rapid intravenous infusion of a half-hour, 1,5 days; Nida platinum Injection 80mg/m2, added 0.9% sodium chloride injection 500ml slow intravenous infusion of 2 hours, one day. Repeated every 4 weeks. After 2 cycles according to WHO criteria to evaluate the efficacy and toxicity. Results Group received a total of 137 cycles treatment, 1 to 6 cycles of each case, an average of 3.8 cycles evaluable for efficacy and side effects. 1 cases CR (2.9%), 12 PR (34.3%). Initial treatment or retreatment, staging, histological type had no effect on short-term efficacy. Common toxicity was myelosuppression. Conclusion vinorelbine combined with nedaplatin treatment of advanced esophageal cancer the exact effect and toxicity can control, is worthy of clinical use.

Key words】 Changchun vinorelbine; nedaplatin; advanced esophageal cancer; treatment

Clinical Observation of Nedaplatin Combined with Vinorelbine in Treating Advanced Esophageal Carcinoma

    HUANG Yong, QIN Shu  kui, HE Ze  ming, QIAN Jun

    Department of Oncology, 81 Hospital of PLA Cancer Center, Nanjing 210002, ChinaAbstract: Objective To evaluate the efficacy and toxicity of nedaplatin combined with vinorelbine in Treating Advanced Esophageal Carcinoma. Methods Thirty  five patients with Advanced Esophageal Carcinoma were treated with nedaplatin 80mg/m2 on days 1 and vinorelbine 25mg/m2 on days 1 and 5 delivered by venous injection. The regimen was repeated more than 2 cycles. WHO crieerias were used to evaluation. Results Gross efficiency rate was 37.1% with 1 cases CR and 12 cases PR. The median TTP was 5.1 months. Toxic effects can be controlled. Conclusion Nedaplatin combined with vinorelbine in Treating Advanced Esophageal Carcinoma had better effective and less toxic effects.

    Key words: Vinorelbine; Nedaplatin; Advanced Esophageal Carcinoma; Treatment

China is the incidence of esophageal cancer in the world and the highest mortality countries, after half a century of exploration and research, the drug treatment of esophageal cancer has greatly improved. Especially the emergence of new drugs, clinical applications the taxane Nedaplatin, and Changchun vinorelbine chemotherapy drug for advanced esophageal more chemotherapy drugs and portfolio choice, effective way to avoid cross-resistance. April 1999 to February 2008, the application of vinorelbine plus nedaplatin treatment of advanced esophageal total of 35 cases, and achieved good effect, are as follows:

    1 Materials and Methods

    1.1 The clinical data

    The entire group of 35 patients, including 22 males and 13 females; aged 39 to 77 years, with a median age of 53 years; All patients had histopathologic and (or) cytological diagnosis is based, including squamous cell carcinoma, 29 cases, glandular carcinoma in 6 cases. Initial treatment of 8 patients, retreatment of 27 patients, including retreatment of patients had one or more chemotherapy regimens applications, including TP (paclitaxel, cisplatin), TF (paclitaxel, fluorouracil), DP (multi docetaxel, cis platinum), DF (docetaxel, fluorouracil) and PF (cisplatin, fluorouracil) programs, but not application of vinorelbine and nedaplatin program, Qiemo chemotherapy time over four weeks away from the treatment time; There was no platinum drug allergies. All patients had imaging measurable tumor lesions, spiral CT scan lesion diameter ≥ 1cm, including liver metastases 15 cases of lung metastases 9 cases, 8 cases of supraclavicular lymph node metastasis, mediastinal lymph node metastases seven cases of local recurrence 5 cases, three cases of abdominal lymph node metastases, bone metastasis in 2 cases. WHO TNM staging: Ⅲ A period of 14 cases 11 cases, 10 cases, Ⅳ stage Ⅲ stage B. Liver and kidney functions are normal, Karnofsky score (KPS) ≥ 60, expected survival ≥ 3 months. The patients were informed consent, voluntarily enrolled for treatment.

    1.2 method of administration and dose

    Nedaplatin injection, 80mg/m2, 0.9% sodium chloride injection, injection, vinorelbine 25mg/m2, adding 0.9% sodium chloride injection 100ml, rapid intravenous infusion of 0.5h, 1,5 days; 500ml, slow intravenous infusion 2h, one day. Repeat every four weeks, before chemotherapy routinely given 5  HT3 receptor antagonist antiemetic treatment.

    1.3 efficacy and toxicity evaluation

    Before and after treatment to check serum tumor markers (CEA), ECG, chest, upper abdominal spiral CT; weekly review of liver and kidney function. Evaluation of recent objective efficacy for the treatment to reach the two cycles or more, according to the 1981 WHO criteria, divided into complete remission (CR), partial remission (PR), stable (SD) and progress (PD), CR + PR (RR); toxicity according to the WHO criteria, divided into 0 ~ Ⅳ degrees.

    2 Results

    The whole group of 35 patients received a total of 137 cycles of therapy, 1 to 6 cycles of each case, an average of 3.8 cycles can be evaluated the efficacy and side effects.

    2.1 The short-term effect

    Whole group one cases of CR (2.9%), 12 PR (34.3%), 16 cases of SD (45.7%), 6 cases of PD (17.1%), response rate (RR) was 37.1% (13/35). Initial treatment or retreatment, staging, pathological type of short-term efficacy had no effect, as shown in Table 1.

    2.2 time to disease progression (TTP)

    Follow-up of 4 to 18 months, all patients the time to disease progression (TTP) for January to December, the median TTP 5.1 months, the naive group median TTP was 6.2 months, the the retreatment group of 4.4 months. , CR cases to achieve CR after four cycles of the chemotherapy and TTP for up to 12 months.

    2.3 toxicity

    Common toxicity to bone marrow suppression, primarily neutropenia, incidence of 65.7%, Ⅲ degree of 14.3%, timely application of G  CSF able to return to normal after treatment, no cases of delayed or reduce treatment medication, hemoglobin, platelet Ⅲ decreased lower. Non-hematologic toxicity was the most common are nausea and vomiting, the incidence of 48.6%, but did not appear serious (Ⅲ IV) nausea and vomiting, symptomatic treatment, or after the end of treatment can alleviate; Other peripheral neuritis, alopecia, skin reactions and other complaints were, were relatively minor, short-lived, as shown in Table 2.

    3 Discussion

    Vinorelbine (vinorelbine, VNB) is a new generation of Changchun bases anticancer drugs are widely used in a variety of solid tumors, non-small cell lung cancer, breast cancer, head and neck cancer. As early as 1996, European scholars Conroy T [1] began VNB trial in the treatment of metastatic esophageal cancer, single-agent objective response rate was 7%, the median progression-free survival time (PFS) 1.9 months, and median overall survival time (OS) 7.8 months. 20 years the VNB-based combination chemotherapy, radiotherapy programs have emerged metastatic esophageal cancer significantly improved. One of the more common joint program VNB combination with cisplatin (PDD). According to Conroy T, et al [2] reported, VNB joint PDD treatment of metastatic esophageal cancer, and 33.8% of the cases were PR, median PFS 3.6 months. PF regimen (cisplatin plus fluorouracil) esophageal carcinoma postoperative adjuvant chemotherapy, metastatic esophageal cancer palliative chemotherapy standard program, the progress of the disease means that cisplatin resistance VNB combined with a certain extent of the non-platinum-based drug programs to avoid resistance. Moroni M, etc. [3] Application VNB joint Bo to neomycin, ammonia A chatter methotrexate second-line treatment of esophageal squamous cell carcinoma, get PR cases by up to 12.7%, 50% of the SD cases, the median PFS 6.47 months; Airoldi M [4] United VNB with more than West he race treatment recurrence of esophageal squamous cell carcinoma, the total effective rate (RR) of 60%, CR 15% (3/20), PR 45% of (9/20), median OS 10.5 months. However, research is still rare program about the VNB joint 3rd generation platinum drugs.

    Nedaplatin (Nedaplatin, NDP) is a second generation organic platinum anti-cancer drug, chemical name: cis  glycolic acid  diamine platinum is the development of a new generation of injectable formulations of platinum in Japan Shionogi Company, its mechanism is into the cells, resulting in the rupture of the bond between an active oxygen and platinum glycolate lipid Peiji, and combine with water, resulting in the formation of ionic substances, the rupture glycolate lipid ligands becomes stable and was release in Table 1 vinorelbine combined Nedaplatin, treatment of esophageal cancer [cases Table 2 vinorelbine plus nedaplatin treatment of esophageal toxicity [Example radiotherapy and produce a variety of ionic substances bind to DNA , and inhibition of DNA replication, thereby generating the anti-cancer activity, the dissolution concentration is about 10 times the PDD [5]. It was reported that the NDP monotherapy esophageal efficiency as high as 51.7% (15/29) [6]. INABA H [7] study the NDP treatment of esophageal cancer than the PDD more effective and less gastrointestinal toxicity. Rui-Hua Xu et al [8] NDP (approval number: 2000XL0208) Ⅱ clinical studies have shown that combined 5  Fu treatment of esophageal cancer was 32.1% (9/28), PDD joint 5  Fu compared with 22.7% (5/22), the difference was statistically significant (P = 0.017). Related to cross-resistance between the NDP and the PDD type of malignancy [9], a Phase II clinical studies have shown that esophageal cancer patients, and between the two there is no cross-resistance [10].

    To this end, our joint VNP and NDP (referred to as NN program) in the treatment of advanced esophageal carcinoma and 35 cases, the overall RR of nearly 40%, and is similar to the reported in the literature. This group, the vast majority of cases of retreatment has application cisplatin, fluorouracil, regular program of multi-line chemotherapy drugs such as paclitaxel and docetaxel group, no the conventional effective drug or programs available on the treatment. Resistance after the switch to the program is still one-third of the cases, nearly half of the cases in stable condition, made prominent effect; efficient de novo cases seems to be higher, and one cases of CR. The rest of the stratified analysis: NN program of squamous cell carcinoma, adenocarcinoma, or different staging of esophageal cancer are effective, efficient similar. The fewer the number of cases in each group stratified group larger gap between the number of cases, the need to expand the number of cases, more stringent test design further confirmed.

    The toxicity of the vast majority of cases are mild, mainly bone marrow suppression, nausea and vomiting, the patient can tolerate, symptomatic treatment does not affect the medication.

    In summary, vinorelbine combined nedaplatin treatment of advanced esophageal cancer has a good effect, able to overcome drug resistance to conventional chemotherapy; moderate toxicity in most cases, is another option for the treatment of advanced esophageal cancer, worthy of clinical trial.