| Objective: To investigate the dose-limiting toxicity(DLT)of the regimen—to treat locally advanced nasopharyngeal carcinoma(NPC)with different dose-levels of lobaplatin weekly along with intensity modulated radiotherapy(IMRT),and define the maximum tolerated dose(MTD).Methods: 1.Patients who were firstly diagnosed with stage ?/IVa locally advanced NPC were enrolled into this study.Concurrent chemoradiotherapy was given to all the patients with dose escalation of lobaplatin weekly and IMRT radical radiotherapy.The initial dose of lobaplatin is 15mg(m2·w)-1.All patients completed at least six cycles chemotherapy while receiving the definite radiotherapy.The adverse reactions were evaluated.Each dose level involved 3 patients.And if no dose-limiting toxicity(DLT)was observed,the test would move to the next dose level and lobaplatin escalated 5(mg·m)-1each time.If one case of DLT appeared at a certain dose level,the same dose level would be repeated in another three cases.If there was no DLT,the escalating test continued,moving to the next dose level.If there was still one case of DLT or originally 2 cases of DLT showed up,the test terminated.The MTD was declared to be one dose level below the level at which DLT appeared..2.Patients undergoing the lobaplatin dose-escalation study were divided into two groups,according to the degrees of myelosuppression.Group 1 refers to cases of myelosuppression at or below Grade ? while Group 2 refers to those at or above Grade ?.We delineated the vertebral bodies(cervical vertebral,part of the thoracic vertebral)for the two groups of patients,and prescribed the plans by following the original ones(there were no significant differences between the prescribed dose in the target area and the organ-limiting dose between two groups).The differences of irradiation dose between the two groups were compared.We chose 3 patients of nasopharyngeal carcinoma(Case1 is T1N3M0 IVa,Case2 is T4N2M0 IVa,Case3 is T2N2M0 III)after the intensity-modulated radiotherapy,defining the radiation dose in the field(D2<45Gy,D10<40Gy)and then recreated the radiotherapy plan,and making the target dose and the dose of other organs at risk the same as the former plans.We analyzed the changes of the parameters,primarily investigating the feasibility of intensity-modulated radiation therapy plan which limited the dose of vertebral bodies.Results: 1.Totally 9 patients were recruited.On the dose levels from 15 to 20 mg(m2·w)-1,no patient experienced DLT.On the next dose level of 25 mg(m2·w)-1,2 out of 3 patients experienced grade ? thrombocytopenia.The experiment terminated.So the MTD was determined as 20mg(m2·w)-1.No grade IV adverse reaction was observed.The complete remission(CR)rate of the positivity of nasopharyngeal and cervical neck lymph node was 89 percent(8/9)after the therapy for 3 months.2.V5?V10?V20?V30?V40?V50?V60?Dmean in group 1 and group 2 were73.9%vs87.4% ? 71.6%vs84.8% ? 68.4%vs79.9% ? 56.6%vs70.1% ?25.0%vs35.5%?10.1%vs12.9%?1.8%vs2.8%?2754.6c Gy vs 3320.5c Gy.We chose 3 cases to be dosimetry-restricted on the vertebral body.The dose of organs at risk exceed the limit dose among Case 1 and Case 2.Case 3 organ at risk dose meets the plan requirements.Conclusion: 1.The MTD of lobaplatin in weekly regimen with concurrent IMRT was 20 mg(m2·w)-1 for locally advanced NPC.The DLT was thrombocytopenia.2.Acute hematologic toxicities may be related to the radiation dose of the vertebral body in nasopharyngeal cancer patients during the radiotherapy.It seems to be clinically feasible to treat those patients,whose specific nasopharyngeal anatomical regions are invaded,with an intensity-modulated radiotherapy plan that defines the vertebral dose. |
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