The Prognostic Factor Analysis and Effect of Adjuvant M-VAC Chemotherapy on Advanced Transitional Cell Carcinoma of the Upper Urinary Tract / 대한비뇨기과학회지

PURPOSE: We evaluated the prognostic factors affecting the patients' survival and analyzed the effect of the adjuvant M-VAC chemotherapy after nephroureterectomy for patients with advanced (T3, T4) transitional cell carcinoma (TCC) of the upper urinary tract (UUT) with compared to surgery only group. MATERIALS AND METHODS: Of 33 patients diagnosed with upper urinary tract transitional cell carcinoma at our institution from 1988 to 1999, 20 patients with advanced transitional cell carcinoma of the renal pelvis and ureter underwent nephroureterectomy and follow-up. 5 patinets were treated nephroureterectomy only, and 15 patients were treated with nephroureterectomy plus adjuvant M-VAC chemotherapy. Prognostic factors such as age, bladder invasion, IVP finding, tumor stage, tumor grade, and tumor multiplicity were investigated. RESULTS: The mean age was 61 years old (38-75). The tumor stage (T3; 10 cases, T4; 10 cases) was not of benefit in predicting survival. Other prognostic factor such as bladder invasion, IVP finding, tumor multiplicity were not correlated with survival rate. The treatment method (nephroureterectomy only group-13.2 months vs. adjuvant M-VAC group-115 months), and tumor grade (GII; 12 cases, 39.2 months vs. GIII; 8 cases, 16.3 months) has significant prognostic value in survival rate. CONCLUSIONS: Many prognostic factors such as age, bladder invasion, IVP finding, stage and tumor multiplicity have no influence on the survival of patients with UUT TCC while tumor grade seems to be correlated with the survival. Survival rate of studied M-VAC group is superior to that of control surgery-only group. So adjuvant M-VAC chemotherapy is the valuable and tolerable treatment moldality in order to prolong the survival time for the patients with high stage UUT TCC.

M-VAC Chemotherapy for Bladder Cancer in Elderly / 대한비뇨기과학회지

PURPOSE: Forty percent of the newly diagnosed bladder cancer patients are over the age of 70 years, but it is said that over 75% of them are excluded from active programs of management. This study was to evaluate the usefulness of M-VAC(methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for invasive bladder cancer patients over the age of 70 years compared with that of patients under the age of 70 years. MATERIALS AND METHODS: Sixty patients with invasive bladder cancer were treated with M-VAC chemotherapy. We divided the patients into group 1- 20 patients over the age of 70 years and group 2- 40 patients under the age of 70 years. We compared cycle length, toxicity and clinical response of M-VAC chemotherapy in group 1 with those of group 2. RESULTS: The Karnofsky performance score was 85.5% in group 1 and 96.3% in group 2. The cycle length needed for 2 cycle of M-VAC chemotherapy was 67.2(range, 56-92) days in Group 1 and 61.5(range, 56-78) days in Group 2(p>0.05). Hematologic toxicities had not significant difference between two groups. Vomiting and stomatitis occurred more common in group 1. In 3 patients of group 1, the serum creatinine level rose to more than 3 mg/dl. The clinical response was 50% in Group 1 and 67% in Group 2(p>0.05). CONCLUSIONS: The bladder cancer patients over the age of 70 years had much more toxicity, longer cycle length and lower response rate, but these differences had not statistical significance. These results suggest that M-VAC chemotherapy in patients over the age of 70 years will achieves the therapeutic effects when the patients have a good physical condition and toxicities to chemotheraphy are monitored closely.

Effect of M-VAC(Methotrexate, Vinblastine, Adriamycin and Cisplatin) Chemotherapy in Locally Invasiue T3a/T3b) Transitional Cell Carcinoma of the Bladder / 대한비뇨기과학회지

PURPOSE: Since a significant number of patients with locally invasive bladder tumor(T3a/T3b) subsequently develop distant metastases, there have been lots of controversies in deciding treatment modalities. In the past decade, progress has been made in the development of effective chemotherapy for the treatment of advanced transitional cell carcinoma of the urothelium. Thus, we reviewed the effectiveness of the M-VAC(methotrexate, vinblastine, adriamycin, and cisplatin) chemotherapy for locally invasive transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: We reviewed 36 patients who were diagnosed as T3a/T3b TCC and treated with aggressive transurethral resection of the bladder tumor(TURBt) and M-VAC chemotherapy Remission was defined in case of complete disappearance of the tumor or downstaging, and progression was defined in case of persistent disease or upstaging. RESULTS: Mean age of the patients was 60.4 years old(33 males; 3 females), and mean follow up was 12.2 +/- 8.9 months. Response rate considering loss of follow up according to the Kaplan-Meyer's method, was 79, 49, 44, 37% at 6, 12, 18, 24th month, respectively. Disease progressions were found in 19 patients during follow up, and the mean duration to progression was 9.2 +/- 5.0(1-19)months. 79% of the patients with disease progression showed progression within 12 months. Lymph node metastases or distant metastases were confirmed in 68% of progressed patients. CONCLUSIONS: M-VAC chemotherapy after aggressive TURBt is limited, but erective treatment modality, and it is also useful in deciding the prognosis of cancer with its responsiveness.

Neoadjuvant M-VAC (Methotrexate, Vinblastine, Adriamycin and Cisplatin) Effect on the Invasive Bladder Tumor / 대한비뇨기과학회지

We evaluated the effect of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy in 63 patients with invasive transitional cell carcinoma of the bladder between January 1987 and December 1993. The patients consisted of 59 male and 4 female. Patient age ranged from 35 to 80 years with a mean of 61.5 years. All patients were given 1-7 cycles(mean 2.7 cycles) of M-VAC chemotherapy and followed for 1 to 8 years. Ten patients(16%) achieved a clinical complete remission(CR), 22(35%) partial remission(PR), 11(17.5%) minor response(MR), 11(17.5%) stabilization(STAB), and 9(14%) progression(PROG). The overall clinical response rate was 51%. Of 22 patients who underwent surgery(radical cystectomy in 15, partial cystectomy in 7), 3 patients(14%) achieved objective pathologic response. The estimated 5-year survival rate according to response of primary tumor to chemotherapy was 86%, 55% in patients with response and non-response, respectively. This difference between the groups was statistically significant(P<0.05). Overall 3-years and 5-years survival rates were 73% and 71%, respectively, and mean survival was 3.1 years. The toxicity of the regimen was generally acceptable, but 79% of the patients experienced myelosuppression, 8% hepatic toxicity and 6% stomatitis. In conclusion, the patients who achieved a clinical response seem to have a better prognosis and neoadjuvant M-VAC chemotherapy may result in bladder preservation for selected patients with muscle invasive bladder cancer.

Effectiveness of Bladder Preservation Treatment For Patients with Superfcially Invasive Bladder Tumor(T2/T3a) / 대한비뇨기과학회지

Radical cystectomy and/or radiotherapy represent the standard treatment for invasive bladder carcinoma. However these approaches are less than ideal since a substantial number of patients have progressive disease and die of metastatic cancer. Then recent treatment modality is trending toward chemotherapy. Therefore, we performed the aggressive transurethral resection of the bladder tumor (TURBt) followed by the combined chemotherapy of methotrexate, vinblastine, doxorubicin and cisplatin(RI-VAC) for conservative treatment of muscle invasive transitional cell carcinoma of the bladder. From July 1990 to March 1995, 41 patients with stage T2 to T4 were entered into the study. Of that patients, 26 completed 4 to 8 cycles of M-VAC and were followed, while 15 were excluded from the study because of incomplete chemotherapy or inadequate follow-up. Median follow-up was 30 months(4-56 months). Median age of the patients was 66 years(range 48 to 85 years). All patients had Karnofsky performance status(KPS) score between 70 and l00. There were 3 patients with clinical stage T2, 8 with T3a, 7 with T3b, 8 with T4. G-CSF(Granulocyte-Colony Stimulating Factor) was used for 19 patients with M-VAC induced leukopenia, thereby allowing the chemotherapy to be complete on schedule. Responses to therapy were evaluated according to standard accepted phase II response criteria. Overall clinical response (complete and partia1) was noted in 15 patients(58%), and no response in 11(42%). Of the patients with T2 and T3a, 9(82%) showed complete and partial response, and of them with T3b and T4, 6(40%) showed complete and partial response. Of 26 patients 21(81%) are alive now. These data suggest that survival was no better than expected following radical cystectomy or radiotherapy in short term follow-up, so far, however systemic M-VAC chemotherapy in combination with radical TURBt is probably expected to provide a high response rate and a better survival with the particular advantage of preserving normal bladder function in patients with superficially invasive bladder tumor(T2/T3a).

M-VAC(Methotrexate, Vinblastine, Doxorubicin and Cisplatinum) Chemotherapy for Metastatic Transitional Cell Carcinoma / 대한비뇨기과학회지

We treated 23 patients with metastatic transitional cell carcinoma with methotrexate, vinblastine, doxorubicin and cisplatinum(M-VAC) chemotherapy from March 1989 to June 1994. The mean age of the patients was 60.0 years old and ranged from 49 years old to 75 years old. They were 18 in male and 5 in female. Complete clinical remission was observed in 5 of 23 patients(21.7%) and 6 patients(26.1%) had a partial remission. An overall objective response rate was 47.8%. The median survival was 12.4 months in all 23 patients, and 20.6 months in 5 complete responder, 8.9 months in non-responder. The duration of survival of the patients with complete remission was prolonged significantly compared to the patients with progression. The progression of disease was in 3 of 4 patients with metastatic bone lesion in effect of M-VAC chemotherapy, but complete clinical remission was 1 of 4 patients. After treatment, complete clinical remission was observed in 5 of 18 patients with metastatic lymph node and 5 patients had a partial remission. The progression of disease was in 1 patient with lung and liver metastatic lesions. Toxicity included moderate to severe myelosuppression that resulted in sepsis in 3 patients and mild to moderately anorexia, vomiting, alopecia and renal dysfunction. It was suggested that M-VAC chemotherapy may be effective as treatment for patients with metastatic transitional cell carcinoma.

Effect of GM-CSF to the M-VAC Chemotherapy Induced Leukopenia in Patients with Urothelial Cancer / 대한비뇨기과학회지

Granulocyte macrophage-colony stimulating factor (GM-CSF) occupies a central position in the regulation of hematopoietic responses. GM-CSF not only signals proliferations of granulocyte-macrophage but also drives these cells into differentiation and activates mature cells of the GM-CSF sensitive lineage. Myelosuppression that is induced by M-VAC (methotrexate, vinblastine, doxorubicin, cisplatinum) chemotherapy brings many problems in successful treatment such as sepsis, dose reduction, delaying the schedule. Granulocyte-macrophage colony stimulating factor is introduced hopefully as a new solution for these problems. So we evaluated the efficacy and safety of GM-CSF in leukopenia induced by M-VAC chemotherapy in patients with urothelial cancer. GM-CSF was administered at 200ug subcutaneously in 10 M-VAC cycles of 6 patients on 5th and 6th day after M-VAC therapy. Sixteen cycles, by which only M-VAC chemotherapy was administered without GM-CSF. of the other 6 patients served as control group. Mean white blood cell count in peripheral blood at M-VAC 2nd day and 15th day was 5,630/mm3 and 4,240/mm3 in GM-CSF administered cycles, 6,58l/mm3and 3,613/mm3 in non GM-CSF administered cycles. There was no delayed cycle in administration of MTX and vinblastine at M-VAC 15th day in the cycles with GM-CSF. There was no significant side effects caused by GM- CSF. The result indicates that GM-CSF can be used safely and effectively against leukopenia after M-VAC chemotherapy of urothelial cancer.

The effect of adjuvant M-VAC(methtrexate, vinblastine, doxorubicin and cisplatin) chemotherapy on advanced transitional cell carcinoma of the upper urinary tract / 대한비뇨기과학회지

We treated 11 patients with advanced transitional cell carcinoma of upper urinary tract with adjuvant M-VAC chemotherapy and their median survival time was compared with 9 patients without M-VAC chemotherapy as e historical group. The total number of cycles per each patient ranged from 1 to 5 with a mean of 3.4. Of these patients, 8 patients could be evaluated for response and 4 patients were responded (2 complete and 2 incomplete. response rate 50%). The median duration of response was 26 months for complete responders and 4.5 months for incomplete responders. The median duration of survival for all chemotherapy group, complete responders, progression and historical control group were 22, 23+, 14 and 21 months. respectively. Median survival was 22 months in all 11 patients. 23+ months in clinical responders, 14 months in progression and 21 months in historical control group. Although overall survival was not prolonged significantly in chemotherapy than the historical control group, M-VAC was effective in small proportion of patients (CR: 2/8). The duration of survival of the patients with complete remission was prolonged significantly.

Preliminary results of M-VAC(methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy for advanced trasitional cell carcinoma of the urothelium / 대한비뇨기과학회지

We reviewed retrospectively 23 patients treated with M-VAC (Methotrexate. Vinblastine, Doxorubicin, Cisplatin) from October 1987 to June 1990 at our hospital to evaluate predictive variables for response to chemotherapy and long term survival free of disease. Treatment consisted of monthly cycles of 30mg. per m2 methotrexate, followed 24 hours later by 3mg. per m2. vinblastine, 30mg. per m2. doxorubicin and 70mg. per m2. cisplatin and concluded with repeat vinblastine and methotrexate on days 15 and 22. The Median number of cycles was 3 (range 2 to 5). Complete plus partial remission were observed in 13 of 23 patients (57%) with a median survival or 13 months (range 7+ to 32+ months). Stabilization occurred in 3 patients (14%) and progression in 7 patients (29%) with median survivals of 10 months (range 7+ to 11 months) and 8 months(4 to 12+ months). 1 year survival rate was 77% in complete puls partial remission and 66% in stabilization and 28% in progression. 10 patients with a complete plus partial remission are alive with a median follow up of 15 months ( range 4 to 32+ months), of whom 1 is surviving for more than 2 years. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 1 patient mild to moderate anorexia, vomiting, alopecia and renal dysfunction. Though the number of availuable patients are limited, these preliminary results suggest that treatment with M-VAC is effective against disseminated urothelial transitional cell tumors.

M-VAC Monotherapy for Advanced Transitional Cell Carcinoma of the Bladder / 대한비뇨기과학회지

We retrospectively reviewed eleven patients with advanced bladder carcinoma (T3b-4) who were treated with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy alone. 1. The mean age and the cycle were 64 years ( 50-75) and 4.7 cycles ( 1-II) respectively. 2. In primary lesions, four (36.4 per cent) showed partial response, six (54.5 per cent) minor response and one (9.1 per cent) clinically stable, and therefore response rate was 36.4 per cent. There was no case of complete remission. In extravesical lesions, progression was seen in a case of liver metastasis and no remarkable changes was seen in bone metastatic case. 3. Maximal effect of clinical response was observed after completion of 3-4 cycles in cases of partial remission. 4. There were marked improvement of clinical symptoms such as loss of hematuria and dysuria during 1 or 2 cycles of chemotherapy. Even though there was no case of complete remission in our cases, 3-4 cycles of M-VAC monotherapy may be considered as a kind of treatment of the advanced transitional cell carcinoma or bladder in selected cases.

The Effect of M-VAC (Methotrexate, vinblastine, Doxorubicin and cisplatin) Chemotherapy for Metastatic Transitional Cell Carcinoma of the bladder Preliminary Report / 대한비뇨기과학회지

We treated 15 patients with metastatic transitional cell carcinoma with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy. Median patient age was 58 years. The site of primary lesion was bladder in all cases. Histologically, these tumors were all identified as transitional cell carcinoma. The average number of cycle were 4.5 and the cycle length varied from 28 days to 94 days (average 38 days). Of these patients, 12 had measurable disease and 6 responded (3 complete and 3 partial remission response rate 50%). Median survival was 10 months in all 16 patients, 17+ months in complete remission and 3.7 months in progression. Complete tumor regression was observed more frequency with local-regional lesions. Toxicity was severe, with 13% of the patient experiencing nadir sepsis, 47% renal toxicity and 20% mucositis. Although overall survival was not prolonged significantly than the historical control group, M-VAC was effective in small proportion of patients (CR : 3/12). The duration of survival of the patients with complete remission was prolonged significantly. Toxicity was severe but tolerable.