• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.76-83
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• 1995

Background: Despite advances in chemotherapy, the treatment of inoperable non-small cell carcinoma of the lung remains poor. According to the recent reports, the response rates of mitomycin, vinblastine, and cisplatin(MVP) chemotherapy are higher than those of other cisplatin based polychemotherapy and MVP chemotherapy can be used as neoadjuvant chemotherapeutic regimen. But the overall response rates of MVP chemotherapy range from 17 to 53 percent, so we studied the effect of MVP chemotherapy in advanced non-small cell lung cancer. Method: We treated forty patients with stage III or IV non-small cell lung cancer with two courses of MVP chemotherapy($8mg/m^2$ of mitomycin on day 1, $6mg/m^2$ of vinblastine on day 2 & day 14, and $100mg/m^2$ of cisplastin on day 1) at 4 weeks interval. Then all patients were evaluated the response of chemotherapy 4 weeks later, and received further chemotherapy, palliative radiotherapy or supportive therapy according to the patient's condition. We also determined the median survival time and prognostic factors. Results: 1) Nine patients(23%) had a partial reponse, 23 patients(57%) had a stable disease, and disease progressed in 8 patients(20%). There were no patients with complete response. 2) The overall median survival time was 36 weeks(range, 9 to 119+ weeks). The median survival time of responder(partial response) and non-responder(stable and progressed) groups were 60 weeks(range, 36 to 82+ weeks) and 31 weeks(range, 9 to 119+ weeks) respectively(p=0.03). 3) The median survival time of the female group was 71 weeks and significantly prolonged in comparision with 35 weeks of the male group(p=0.01). But, the other prognostic factors didn't affect the survival time and response rate. 4) The median survival times of chemotherapy group and chemotherapy with palliative radiotherapy group were not significantly different. Conclusion: MVP combined chemotherapy is unsatisfactory in improving survival in advanced non-small cell lung cancer. Therefore, further studies are needed to find more active new agents and to estabilish the efficacy of the combined treatment with radiotherapy and/or surgery.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.215-219
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• 1991

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991, Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGy following 3 cycles of induction MVP (Mitomycin C 6 mg/$m^2$, Vinblastine 6 mg/$m^2$, Cisplatin 60 mg/$m^2$) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 46 were analyzed for this preliminary report. The response rate of induction chemotherapy was $62.5\%$ : partial response, $50\%$ and minimal response, $12.5\%$. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.149-156
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• 1995

Purpose : Since February 1991 a Prospective study for non-small cell lung cancer patients who underwent radical resection and had a risk factor of positive resection margin or regional lymph node metastasis has been conducted to evaluate the effect of MVP chemotherapy and radiotherapy on the pattern of failure, disease free and overall survival. and tolerance of combined treatment. Materials and Methods: Twenty nine patients were registered to this study until Sep. 1993; of these 26 received planned therapy Within 3 weeks after radical resection, two cycles of MVP(Mitomycin C $6mg/m^2,$ Vinblastin $6mg/m^2,$ Cisplatin $60mg/m^2$) chemotherapy was given with 4 weeks intervals. Radiotherapy (5040cGy tumor bed dose and 900cGy boost to high risk area) was started 3 to 4 weeks after chemotherapy. Results: One and two year overall survival rates were $76.5\%\;and\;58.6\%$ respectively. Locoregional failure developed in 6 patients$(23.1\%)$ and distant failure in 9 patients$(34.6\%)$ Number of involved lymph nodes, resection margin positivity showed some correlation with failure pattern but T-stage and N-stage showed no statistical significance. The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy within 70 days showed lower incidence of distant metastasis. Postoperative combined therapy were well tolerated without definite increase of complication rate, and compliance rate in this study was $90\%$. Conclusion: 1) MVP chemotherapy showed no effect on locoregional recurrence, but appeared to decrease the distant metastasis rate and 2) combined treatments were well tolerated in all patients. 3) The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy within 70days showed lower incidence of distant metastasis. 4) Addition of chemotherapy to radiotherapy failed to increase the overall or disease free survival.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.195-202
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• 1999

Purpose : We peformed this study to evaluate the prognostic factors and the effect of induction chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and Methods : A retrospective analysis was done for 130 patients with locally advanced NSCLC treated with curative radiotherapy alone or induction chemo-radiotherapy from January 1986 to October 1996. Eighty-five patients were treated with radiotherapy alone, forty-five with induction chemotherapy and radiotherapy. Age, sex, performance status, histopathologic type, and stage were evenly distributed in both groups. The patients were treated with 6 MV or 10 MV X-ray. Conventional fractionation with daily fraction size 1$.8\~2.0$ Gy was done. Of the patients, 129 patients received total dose above 59.6 Gy ($56\~66$ Gy, median 60 Gy). Induction chemotherapy regimen were CAP (Cyclo-phosphamide, Adriamycin, Cisplatin) in 6 patients, MVP (Mitomycin, Vinblastine, Cisplatin) in 9 patients, MIC (Mitomycin, Ifosfamide Cisplatin) in 13 patients, and EP (Etoposide, Cisplatin) in 17 patients. Chemotherapy was done in $2\~5$ cycles (median 2). Results : Overall 1-, 2-, and 3-year survival rate (YSR) for all patients were $41.5\%,{\;}13.7\%,{\;}and{\;}7\%$, respectively (median survival time 11 months). According to treatment modality, median survival time, overall 1-, 2-, and 3-YSR were 9 months, $32.9\%,{\;}10.\5%,{\;}6\%$ for radiotherapy alone group, and 14 months, $57.8\%,{\;}20\%,{\;}7.6\%$ for induction chemotherapy group, respectively (f=0.0005). Complete response (CR) to overall treatments was $25\%$ (21/84) in radiotherapy alone and $40.5\%$ (17/42) in induction chemotherapy group (p=0.09). The Prognostic factors affecting overall survival were hemoglobin level (p=0.04), NSE (neuron-specific enolase) level (p=0.004), and respense to overall treatment(p=0.004). According to treatment modalities, NSE (neuron-specific enolase) (p=0.006) and response to overall treatment (p=0.003) were associated with overall survival in radiotherapy alone group, and response to overall treatment (p=0.007) in induction chemotherapy group. The failure Pattern analysis revealed no significant difference between treatment modalities. But, in patients with CR to overall treatment, distant metastasis were found in 11/19 patients with radiotherapy alone, and 3/13 patients with induction chemotherapy and radiotherapy (p=0.07). Locoregional failure patterns were not different between two groups (10/19 vs 6/13). Conclusion : Induction chemotherapy and radiotherapy achieved increased 2YSR compared to radiotherapy alone, At least in CR patients, there was decreased tendency in distant metastasis with induction chemotherapy. But, locoregional failures and long-term survival were not improved. Thus, there is need of more effort to increasing local control and further decreasing distant metastasis.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.265-274
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• 1998

Purpose : This prospective study has been conducted to assess the value of three dimensional conformal radiation therapy (3DCRT) for lung cancer and to determine its potential advantage over current treatment approaches. Specific aims of this study were to 1) find the most ideal 3DCRT technique 2) establish the maximum tolerance dose that can be delivered with 3DCRT and 3) identify patients at risk for development of radiation pneumonitis. Materials and Methods : Beginning in Nov. 1994, 95 patients with inoperable non-small cell lung cancer (stage I; 4, stage II; 1, stage IIIa; 14, stage IIIb; 76) were entered onto this 3D conformal trial Areas of known disease and elective nodal areas were initially treated to 45 Gy and then using 3DCRT technique 65 to 70 Gy of total dose were delivered to the gross disease. Sixty nine patients received 65 Gy of total dose and 26 received 70 Gy Seventy eight patients (82.1$\%$) also received concurrent MVP chemotherapy. 3DCRT plans were compared with 2D plans to assess the adequacy of dose delivery to target volume, dose volume histograms for normal tissue, and normal tissue complication Probabilities (NTCP). Results : Most of plans (78/95) were composed of non-coplanar multiple (4-8) fields. Coplanar segmented conformal therapy was used in 17 pateints, choosing the proper gantry angle which minimize normal lung exposure in each segment. 3DCRT gave the full dose to nearly 100$\%$ of the gross disease target volume in all patients. The mean NTCP for ipsilateral lung with 3DCRT (range; 0.17-0.43) was 68$\%$ of the mean NTCP with 2D treatment planning (range; 0.27-0.66). DVH analysis for heart showed that irradiated volume of heart could be significantly reduced by non-coplanar 3D approach especially in the case of left lower lobe lesion. Of 95 patients evaluable for response, 75 (79$\%$), showed major response including 25 (26$\%$) with complete responses and 50 (53$\%$) with partial responses. One and two rear overall survivals of stage III patients were 62.6$\%$ and 35.2$\%$ respectively. Twenty percent (19/95) of patients had pneumonitis; Eight patients had grade 1 pneumonitis and 11 other patients had grade 2. Comparison of the average of NTCP for lung showed a significant difference between patients with and without radiation pneumonitis. Average NTCP for Patients without complication was 62$\%$ of those with complications. Conclusions : This study showed that non-coplanar multiple fields (4-8) may be one of the ideal plans for 3DCRT for lung cancer. It also suggested that 3DCRT may provide superior delivery of high dose radiation with reduced risk to normal tissue and that NTCP can be used as a guideline for the dose escalation.