• Radiation Oncology Journal
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• v.19 no.3
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• pp.237-244
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• 2001

Purpose : To assess the tolerance, complete response rate, bladder preservation rate and survival rate in patients with muscle-invading bladder cancer treated with selective bladder preservation protocol. Method and Materials : From October 1990 to June 1998, twenty six patients with muscle-invading bladder cancer (clinical stage T2-4, N0-3, M0) were enrolled for the treatment protocol of bladder preservation. They were treated with maximal TURBT (transurethral resection of bladder tumor) and 2 cycles of MCV chemotherapy (methotrexate, crisplatin, and vinblastine) followed by $39.6\~45\;Gy$ pelvic irradiation with concomitant cisplatin. After complete urologic evaluation (biopsy or cytology), the patients who achieved complete response were planed for bladder preservation treatment and treated with consolidation cisplatin and radiotherapy (19.8 Gy). The patients who had incomplete response were planed to immediate radical cystectomy. If they refused radical cystectomy, they were treated either with TURBT followed by MCV or cisplatin chemotherapy and radiotherapy. The median follow-up duration is 49.5 months. Results : The Patients with stage T2-3a and T3b-4a underwent complete removal of tumor or gross tumor removal by TURBT, respectively. Twenty one out of 26 patients $(81\%)$ successfully completed the protocol of the planned chemo-radiotherapy. Seven patients had documented complete response. Six of them were treated with additional consolidation cisplatin and radiotherapy. One patient was treated with 2 cycles of MCV chemotherapy due to refusal of chemo-radiotherapy. Five of 7 complete responders had functioning tumor-free bladder. Fourteen patients of incomplete responders were further treated with one of the followings : radical cystectomy (1 patient), or TURBT and 2 cycles of MCV chemotherapy (3 patients), or cisplatin and radiotherapy (10 patients). Thirteen patients of them were not treated with planned radical cystectomy due to patients' refusal (9 patients) or underlying medical problems (4 patients). Among twenty one patients, 12 patients $(58\%)$ were alive with their preserved bladder, 8 patients died with the disease, 1 patient died of intercurrent disease. The 5 years actuarial survival rates according to CR and PR after MCV chemotherapy and cisplatin chemoradiotherapy were $80\%\;and\;14\%$, respectively (u=0.001). Conclusion : In selected patients with muscle-invading bladder cancer, the bladder preservation could be achieved by MCV chemotherapy and cisplatin chemo-radiotherapy. All patients tolerated well this bladder preservation protoco. The availability of complete TURBT and the responsibility of neoadjuvant chemotherapy and chemoradiotherapy were important predictors for bladder preservation and survival. The patients who had not achieved complete response after neoadjuvant chemotherapy and chemoradiotherapy should be immediate radical cystectomy. A randomized prospective trial might be essential to determine more accurate indications between cystectomy or bladder preservation.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.