A Clinical Comparison Of PEA Protocol For Treatment Of Gestational Trophoblastic Neoplasms With 5-Fu+KSM Protocol

Gestational trophoblastic neoplasms is a type of highly malignant tumors. gestational trophoblastic neoplasms were treated by operation, before the effective chemotherapy drugs were founded,with a higher mortality rate.2-year survival rate of patients with invasive mole treated by simple hysterectom was 40%, while only 15% in patients with choriocarcinoma. Until 1956, Li and so introduced the effective chemotherapy drugs, Professor Song Hongzhao created including single-drug 5-Fu, 5-Fu + KSM and other treatment protocol, the treatment of gestational trophoblastic neoplasms had a revolutionary change, through Chemotherapy, the cure rate of cases without metastasis can reach 100%, The total cure rate can reach 80% -90%. Due to the highly sensitive to chemotherapy of gestational trophoblastic neoplasms and the high sensitivity and specificity of human chorionic gonadotropin (HCG) to monitor tumor, gestational trophoblastic neoplasms have the best prognosis,to become one of the earliest solid tumors which can be cured. Currently we often use fluorouracil combination chemotherapy with genshammycin,and had achieve good curative effect. However, these treatment protocol originated in our country achieved good effect, but side effects are more serious.5-Fu with low bioavailability. Only a small part of 5-Fu play a role in killing tumor cells, Its side effects is highly significant. Mainly in bone marrow suppression and gastrointestinal symptoms significantly. Severe bone marrow suppression may predispose to sepsis, septic shock can be fatal in severe. Gastrointestinal symptoms such as nausea, vomiting, gastrointestinal ulcer, oral ulcers, diarrhea, etc., so that patients depression, poor appetite, water and electrolyte disturbance, If not handled properly can be complicated by pseudomembranous colitis, and might cause death. The course of 5-Fu+KSM chemotherapy is 8 days, Because of the short half-life of 5-Fu, only 10-20 min, in order to maintain the steady-state concentration of long, continuous infusion is often taken for drug delivery, This treatment protocol need more than 12 hours per day, And intravenous injection can injury the peripheral vascular, if continuous intravenous infusion of central venous catheter may cause infection and thrombosis, this treatment protocol seriously decreased the quality of life of patients and increased treatment costs. Serious side reaction lead to the interrupted or failure or delay of chemotherapy in some patients. Some patient give up the treatment due to unbearable the side effects of chemotherapy, has poor compliance. There is also a problem of drug resistance. It was reported that using the PEA protocol as the first choice for high-risk GTN, and had achieve good effect. Since February 2008, we have use the PEA protocol for treatment of gestational trophoblastic neoplasms and achieved good effect. This paper retrospectively analyzed 62 cases of gestational trophoblastic neoplasms from July 2004 to November 2009 in our hospital. Through the evaluation by comparing the treatment efficacy and side effects of these two protocols, to explore whether the PEA protocol can be used as the first-line chemotherapy drug for gestational trophoblastic neoplasms.Materials and Methods1. Patient dataSelect 62 patients of gestational trophoblastic neoplasms which were treated in Shengjing Hospital of China Medical University from July 2004 to November 2009. Patients aged 17 to 54 years old, mean age 32.5 years, and 17 to 19 years in 3 cases,20 to 29 years in 29 cases,30 to 39 years in 11 cases,40 to 49 years in 14 patients,50-54 years in 5 cases. The blood human chorionic gonadotropin (HCG) of all cases were higher than normal, and were confirmed by pelvic ultrasonography, chest radiograph or lung CT examination. All patients were in accordance with FIGO.2000 anatomical scoring system and prognosis scoring system for staging. The prognostic score is divided into low-risk score≤6,≥7 were divided into high.30 cases in group of PEA protocol,14 cases in PhaseⅠ,1 case in PhaseⅡ,15 cases in PhaseⅢ; 22 cases of invasive mole, choriocarcinoma 8 cases; 23 cases of low-risk, high-risk 7 cases.32 cases in group of 5-Fu+KSM protocol,16 cases in PhaseⅠ,1 case in Phase II,15 cases in Phase III; 28 cases of invasive mole, choriocarcinoma 4 cases; 22 cases of low-risk, high-risk 10 cases.2. Treatment methodsPEA protocol:Cisplatin (DDP):30mg/m2/d, intravenous infusion of 1 to 3 days, Etoposide (VP-16):100mg/d, intravenous infusion of 1 to 4 days, genshammycin (KSM):8ug/kg/d, intravenous infusion of 1 to 3 days. Interval of treatment was 3 weeks.5-Fu+KSM protocol:fluorouracil(5-Fu):26mg/kg/d, intravenous infusion (≥6h) of 1 to 8 days, genshammycin (KSM):6μg/kg/d, intravenous infusion (> 4-6h) of 1 to 8 days. Interval of treatment was 3 weeks. Withdrawal indications:After the symptoms and signs disappeared, primary and metastatic lesions disappeared and HCG dropped to normal, low-risk patients need to consolidate a course of treatment, high risk onsolidation need to consolidate 2-3 course of treatment.3. Evaluation of efficacy and side effectsAccording to standards of gestational trophoblastic disease after treatment and WHO Clinical evaluation of anticancer drugs in acute and subacute toxicity to evaluate the efficacy and side effects of the two protocols.4. Statistical methodsData were analyzed using SPSS software, data constitute the differences were compared usingχ2 test, P<0.05 was statistically significant.Results1. The complete remission rate of PEA protocol and 5-Fu+KSM protocol was 76.67% and 71.88% respectively, the effective rate was 96.67% and 100%(P>0.05) has no significant difference in efficacy. The period that serum HCG dropped to nomal and total treatment time of PEA protocol were less than 5-Fu+KSM protocol. 2. There were certain side effects in both groups. The incidence rate of marrow suppression was 73.33% (PEA) and 81.25% (5-Fu+KSM) respectively; The incidence rate of III-IV marrow suppression was 16.67% (PEA) and 40.63%(5-Fu+KSM) (P <0.05,have significant difference) respectively; The incidence rate of nausea and vomiting was 90% (PEA) and 100% (5-Fu+KSM) (P>0.05, have no significant difference) respectively; The incidence rate of impairment of the liver or kidney was 43.33% (PEA) and 62.5% (5-Fu+KSM) (P>0.05, have no significant difference) respectively; but the PEA group has lower incidence rate and severity than 5-Fu+KSM group; The incidence rate of oral cavity ulcer of PEA group was 3.33%,lower than 5-Fu+KSM group 81.25% (P<0.05, have significant difference) significantly. The incidence rate of diarrhea of PEA group was 13.33%, lower than 5-Fu+KSM group 68.75%(P<0.05, have significant difference).3. In other aspects, PEA group has shorter duration of average hospital stay, chemotherapy time and treatment costs.ConclusionThe overall effect of PEA protocol showed no significant difference compared with 5-Fu+KSM protocol for the treatment of gestational trophoblastic neoplasms. Two groups have no significant difference in impairment of the liver or kidney, but the PEA group has lower incidence rate and severity than 5-Fu+ KSM group. The incidence of severe bone marrow suppression, gastrointestinal reactions and oral ulcers in PEA group was less than 5-Fu + KSM group. PEA protocol has short duration of average hospital stay, chemotherapy time and treatment costs, is more easily accepted by patients, has good compliance, can be used as first-line chemotherapy drug to further promote in clinical.