- Email: [email protected]
Early whole brain concomitant radiotherapy-chemotherapy for non-small cell lung cancer (NSCLC) brain metastases. A phase 2 study
l O0
Combined Modality Therapy
local progression free survival was 65.4% at 1 year, 42.1% at 2 years and 36.3% at 4 years. Actuarial distant free survival was 58.4% at 1 year, 48.8% at 2 years and 41.1% at 4 years. Severe weight loss (more than 10%) occurred in 20 patients (13.7%) during treatment. Forty two patients (29%) showed radiation pneumonitis; 29 showed grade 1 and 13 other showed grade 2. The average NTCP value of the patients who showed radiation pneumonitis was significantly higher than that of the patients without pneumonitis (66.0% vs. 26.4). Four patients died of treatment related toxicity. This hyperfractionated 3D conformal radiotherapy and concurrent chemotherapy is a well tolerated regimen with acceptable toxicity. This study showed a higher local control rate, and better survival at 2 and 4 years compared to our previous trial of hyperfractionated radiotherapy following 3 cycles of induction chemotherapy.
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2
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•
A
phase IIII study of Docetaxel (Taxotere) combined with concurrent radiation therapy in locally advanced non-small cell lung cancer (NSCLC)
S Aamdal I , G. Lauvvang I , K Owre 1, R. Hatlevoll 1, J. Armellini 2 I Norwegian Radium Hospital, Montebello, Oslo, Norway, 2Aventis, Antony, France Concurrent radiation and chemotherapy play an important role in the treatment of unresectabte NSCLC. We performed a phase 1/11study of Docetaxel (D), 1 h i.v. infusion given at days 1, 8, 22, 29 with concurrent radiotherapy of 2 Gy, 5 days/week (wk) for 5 wks in patients (pts) who were chemotherapy and radiotherapy naive with unresectable stage III NSCLC. Results: 42 pts entered the study, M/F ratio: 27/15, median age: 59 (41-71), median WHO PS: 1 (0-1), histology: squamous 45%, adenocarcinoma 38%, other 17%. 12 pts entered the phase I, the maximum tolerated dose was reached at D 40 mg/m 2, reversible oesophagitis was the dose limiting toxicity. 33 pts have been treated at the recommended dose of D 30 mg/m 2, 1 pt was ineligible (kidney metastasis). Among the 24 pts evaluable for response, an objective response rate (ORR) of 62.5% (95% CI: 40.6-81.2) was observed (8 CR, 7 PR) and confirmed by external expert review. At the recommended dose, the median survival time is 13.6 months (95% Ch 8.2-24.8), the one-year survival is 59.4% (95% CI: 40.6-76.3) and the median time to progression is 12 months (95% CI: 5.1-36.0). The median duration of response (ORR) is 104.6 wks (95% CI: 52.0156.3). The median follow-up period is 9 months (95% Ch 3.3-33.2). 122 cycles were administered (median = 4, range 1-4). The median relative dose intensity was 100%. All pts (N = 33) were evaluable for safety. No grade 3-4 hematological toxicity was observed. Nonhematological side effects: 78% of pts experienced mild to moderate dysphagia, grade 3-4:1 infection, 1 stomatitis, 1 myocardial infarction (recovered), 1 dyspnea, 1 nausea and 1 neuropathy were observed. Conclusion: Docetaxel 30 mg/m 2 weekly for 4 weeks with concurrent radiotherapy (50 Gy) is effective and well tolerated. The simplicity of this chemoradiation regimen facilitates its use for standard stage Ill NSCLC chemotherapy na'~'vepts radiation treatment routines. A phase III randomized comparative trial is ongoing.
Thursday, 14 S e p t e m b e r 2000
8:30-10:00
ORAL SESSION
Combined
•2-•
Modality Therapy
Outcome results of long term follow up, for population based cohort of patients with stage Ilia NSCLC treated with aggressive combined modality treatment approach in a prospective study
S El-Sayed, A Leylek, M Akra, C. Mihalcioiu. University of Manitoba, Winnipeg, Canada
Introduction: Lung cancer is the leading cause of cancer deaths worldwide, historically Radiotherapy was the standard treatment for locally advanced NSCLC producing 5 years disease free survival of around 5%. Recent studies have shown that AGGRESSIVE COMBINED MODALITY treatment is superior to radiotherapy alone in prolonging survival. Objectives: To evaluate the feasibility and potential value of concomitant radiation and chemotherapy followed with surgery in improving the outcome of patients with stage IliA NSCLC in a prospective study setting. The primary end point of the study is Toxicity of the combined modality treatment. Methods: ELIGIBILITY: Patients selected for the study were deemed to have stage IliA, histologically confirmed NSCLC. performance status (KPS) of = or >70%, acceptable pulmonary and renal functions, and signed informed consent. TREATMENT REGIMEN: Treatment included Radiotherapy of 5000 cgy/20 F, days 1-28 in case of small volume or 3500 cgy/10 F, days 1-14 in case of large volume, combined with concomitant chemotherapy with cisplatinum 50 mg/m2 IVI day 1-5, 21-25. Results: From July 1991 to November 1995, 30 patients were accrued with age range of 40-71 years and average age of 59 years. Histology: 14 patients with adenocarcinoma, 8 with squamous cell carcinoma and 8 with poorly differentiated tumors. The majority of the patients presented with cough and dyspnea, some were asymptomatic at presentation. Most of the patients received the planned chemo/radiotherapy. While 9 patients had radical surgery (Iobectomy or pneumonectomy). Toxicity While all patients have required hospitalization for the 5 days of concomitant chemo-radiation, overall, the toxicity of the treatment was mild with no treatment-related death or delay in radiotherapy treatments. SURVIVAL Out of the 30 patients 28 died of their disease and 2 lost to follow up after 15 and 25 months. The median survival is 16 months. Conclusions: The treatment protocol is practical and feasible. The treated patients were more advanced than the average. No doubt that aggressive combined modality treatment prolong survival but distant metastasis remains the main cause of treatment failure. Long term disease free survival remains poor. It is possible that more aggressive chemo/radiotherapy schedules could produce better results. ~ - 9 - ] Early whole brain concomitant radiotherapy-chemotherapy for non-small cell lung cancer (NSCLC) brain metastases. A phase 2 study C. Ngo Quy 1, M.-A. Hailer 1, A. Darut-Jouve 2, G. Jolimoy2, D. Spa~th 3, V. Beckendorf3, T. Bazarbachi 1, E. Luporsi 3, B. Coudert 2, Y. Martinet 1. I Fed6ration de Pneumologie, H6pital de Brabois, Nancy; 2Service d'Oncologie Medicale, Centre Anticancereux G.F. Leclerc, Dijon; 3 Centre Anticancereux A. Vautrin, Vandoeuvre-les-Nancy, France Brain is a frequent secondary location in NSCLC. The combination of chemotherapy (CT) and radiotherapy could increase treatment efficiency by interfering with the cell ability to repair the specific injuries induced by each treatment.
Combined Modafi~ Therapy We have evaluated in an open, non-randomized, prospective, multicenter study, the toxicity and the efficiency of concomitant whole brain radiotherapy (WBRT) (3 Gy x 10 fractions during the first CT cycle) and CT [cisplatin 100 mg/m 2 day (d) 1, oral etoposide 50-100 mg/d (dl to d14), 3 21 d cycles] in NSCLC brain metastases. Toxicity and neurological function were rated according to the WHO criteria and the Order scale. Efficiency was assessed by CT Scan after 3 CT cycles. Patients (pts) were followed every 3 months. Sixteen pts were included, 3 were non evaluable (2 refusals after the consent, 1 accidental loss of patient's file), 13 evaluable: 11 men, 2 women; median age 54 y; 8 adenocarcinoma, 2 squamous cell carcinoma, 2 undifferenciated, 1 large cell carcinoma. At the brain level, 7 objective responses (3 complete), 4 stabilisations and 2 progression were observed. The global response was: 3 partial responses, 7 stabilisations and 3 progressions. The toxicity was: neutropenia: 2 pts grade 3, 5 pts grade 4 (4 sepsis); nausea: 2 pts grade 3, 1 pt grade 4; alopecia: 10 pts grade 3; hearing loss: 2 pts; intracranial hypertension increased in 3 pts during WBRT but was controlled by medical treatment in 2 pts. Neurological function was improved in 4 pts, stable in 6, and worsened in 3. In sept. 99, 9 pts were dead (4 pts died of brain progression and 5 pts died of thoracic progression) with a median survival (MS) of 40.1 weeks (w) (range: 4.3-78.9 w), without brain progression of 26.3 w (range: 0-59.6 w), and without disease progression of 16.1 w (range: 0-34.1 w); 4 pts are still alive, with a median follow-up of 40.6 w (range: 37.7-47.3 w), a MS without brain progression of 39.5 w (range: 25.7-47.3 w), and without disease progression of 31.4 w (range: 21.6-47.3 w). These results show an acceptable toxicity, an encouraging brain objective response rate and survival, and justify to carry on the study.
[-3-~ Brain metastases of lung cancer: Long-term results after concurrent chemoradiotherapy with cisplatin-etoposide F. Reboul, ¥. Brewer, P Vincent, B. Chauvet, C.F. Felix Faure, M. Taulelle. Lung Unit, Institut Sainte Catherine, Avignon, France Brain metastases (BM) are a major problem in patients (pts) with lung cancer, especially when local control has been achieved after combined modality therapy. Results of whole brain radiation therapy (WBRT) are unsatifactory with an average expected survival of 4 months. Chemotherapy (CT) with cisplatin-etoposide (PE) is active against BM with response rates of 20-30%. PE also shows radiosensitizing properties when administered concurrently with radiation. We hypothesized that concurrent WBRT + PE could improve local brain tumor control over WBRT alone in patients with inoperable BM. Methods: Treatment consisted of WBRT (36 Gy in 15 fractions over 3 weeks) with concurrent PE administered once during the 2 nd week of WBRT (P 20 mg/m2/d + E 50 mg/m2/d for 5 days). No additional CT was given after this 3-week treatment. Results: From 01/94 to 04/98, 78 consecutive pts were propectively treated according to this regimen. Characteristics: median age 63.8 years, sex-ratio 6.8, WHO status 2-3 57.7%, adenocarcinoma 41% Median BM diameter was 20 mm with 52.5% multiple BM. Median time from the diagnosis of lung cancer was 7.2 mo with 73% occuring within the first 12 mo. Toxicity was mild, with less than 10% Grade 3-4 adverse events, except universal alopecia. Complete radiological response was observed in 28 pts (36%). With a median follow-up of 46.8 mo, median survival was 7 mo with an overall survival at 1, 2 3 and 4 years of 24.4%, 12%, 10% and 10%, respectively. Definitive control of BM was observed in 73% of pts. Median survival was significantly better (p < .0001) in patients with WHO status 0-1 (11.4 mo), local control of the primary tumor (11.2 mo), complete radiologic response (14.3 mo) and a disease-free interval > 12 months (20.6 mo). After multivariate analysis, WHO status and disease-free interval > 12 mo were the only significant factors for long-term survival (32.6% at 4 years). There was no significant neuro-cognitive impairment in longterm survivors. Conclusions: Combined WBRT + concurrent PE significantly improves control of BM with an encouraging proportion of long-term survivors and should be compared in a randomized trial with WBRT alone or combined with radiosurgery.
101
I - ~ ~ Sequential chemotherapy and radiotherapy in non-small cell lung cancer LF.L Gaspar, RM.C. Susano, M Ortiz, E. Teixeira, R. Sotto-Mayor.
Santa Maria University Hospital, Lisbon; Elvas Hospital, Elves, Portugal Purpose: To evaluate median survival overall survival local progression-free survival and distant progression-free survival. Materials and Methods: One hundred patients with stage III nonsmall cell lung cancer (NSCLC) and Karnofsky Index > 70 were treated from 1992 to 1998 with a sequential approach of chemotherapy (CT) and radiotherapy (RT). 90 male and 10 female; median age = 64.5 years (range 38-77); 24 in stage IliA and 76 in stage IIIB; 46 squamous cell carcinomas, 34 adenocarcinomas, 3 mixed turnouts, 16 unclassified NSCLC and 1 large cell carcinoma. 3 or 4 cycles of CT were performed, 23 patients with mitomicin + vindesine + cisplatin (MVP), 58 with mitomicin + ifosfamide + cisplatin (MIP), 14 with vinorelbine + ifosfamide + cisplatin (NIP) and 5 with gemcitabine + cisplatin (GP); CT was followed by RT in conventional fractionation, 60 Gy/6 weeks; 8 patients underwent a total dose < 60 Gy due to poor performance status and/or disease progression. Results: Median survival = 17 months without statistic significance according to histology: 17 months in squamous cell carcinomas and 14 months in adenocarcinomas (p = 0.6), according to stage: 23 months in IliA and 16 months in IIIB (p = 0.16), according to type of CT: 18 months with MVP, 17 months with MIP, 15 months with NIP and 10 months with GP (p = 0.79) and according to RT dose: 17 months with 60 Gy and 9 months with <60 Gy (p = 0.069). Overall survival at 1 and 2 years is 69.2% and 36% respectively and survival probability at 3 and 5 years is 23.3% and 11.6% respectively. Median time to local progression is 15 months and local progression-free survival at 1, 2 and 3 years is 65.9%, 28.7% and 26.7% respectively. Median time to distant progression is 17 months and distant progression-free survival at 1, 2 and 3 years is 58.8%, 38.2% and 34.2% respectively; brain is the most frequent site of dissemination (37%), followed by bone (33.3%), lung (16.6%) and liver (13%). Overall survival results according to stage, histology and type of CT will also be presented. Conclusion: These results are similar to those published in randomized studies. Distant progression is more likely to occur during the first year and local progression is more frequent during the second year. At this time, there are no differences between CT schemes, although the recent ones (NIP and GP) include few patients. A concomitant approach of CT and RT with an acceptable toxicity might achieve better results in NSCLC.
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Carboplatinlpaclitaxel (C/P) or carboplatinlvinorelbine (CN) followed by accelerated hyperfractionated conformal radiation therapy (AHCRT): A phase I dose esclation trial from the Carolina conformal therapy consortium
L.B. Marks, MA. Socinski, J. Garst, G.S. Sibley, W. Blackstock, A. Turrisi, J. Herndon, S. Zhou, M Anscher, J. Crawford, J. Rosenman. Duke University, Durham, North Carolina; UNC Chapel
Hill, Chapel Hill, North Carolina, USA Combined modality therapy is the standard of care for patients (pts) with unresectable stage III NSCLC. The optimal radiotherapeutic strategy is not known. Conformal planning techniques allow enhanced tumor targeting and the possibility of delivering higher doses with acceptable toxicity. This trial is designed to assess the maximum tolerated dose (MTD) of AHCRT at 1.6 Gy BID following either induction C/P or C N for unresectable IIB-IIIB NSCLC. The initial dose of AHCRT was 73.6 Gy planned conformally (PLUNC: Plan Univ. of North Carolina). Regional lymph nodes received a minimum of 1.25 Gy BID to 45 Gy. All areas of gross disease received 1.6 Gy BID. Patients were enrolled in groups of 14, with AHCRT doses escalated in 6.4 Gy intervals (73.6 Gy, 80 Gy, 86.4 Gy and 92.8 Gy), Within each cohort, 7 received induction C/P and 7 received induction CN. The C/P and C N cohorts were considered separately so as to evaluate the impact of the induction regimen on the rate of grade 3 toxicity, and thus the
Combined Modality Therapy
local progression free survival was 65.4% at 1 year, 42.1% at 2 years and 36.3% at 4 years. Actuarial distant free survival was 58.4% at 1 year, 48.8% at 2 years and 41.1% at 4 years. Severe weight loss (more than 10%) occurred in 20 patients (13.7%) during treatment. Forty two patients (29%) showed radiation pneumonitis; 29 showed grade 1 and 13 other showed grade 2. The average NTCP value of the patients who showed radiation pneumonitis was significantly higher than that of the patients without pneumonitis (66.0% vs. 26.4). Four patients died of treatment related toxicity. This hyperfractionated 3D conformal radiotherapy and concurrent chemotherapy is a well tolerated regimen with acceptable toxicity. This study showed a higher local control rate, and better survival at 2 and 4 years compared to our previous trial of hyperfractionated radiotherapy following 3 cycles of induction chemotherapy.
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A
phase IIII study of Docetaxel (Taxotere) combined with concurrent radiation therapy in locally advanced non-small cell lung cancer (NSCLC)
S Aamdal I , G. Lauvvang I , K Owre 1, R. Hatlevoll 1, J. Armellini 2 I Norwegian Radium Hospital, Montebello, Oslo, Norway, 2Aventis, Antony, France Concurrent radiation and chemotherapy play an important role in the treatment of unresectabte NSCLC. We performed a phase 1/11study of Docetaxel (D), 1 h i.v. infusion given at days 1, 8, 22, 29 with concurrent radiotherapy of 2 Gy, 5 days/week (wk) for 5 wks in patients (pts) who were chemotherapy and radiotherapy naive with unresectable stage III NSCLC. Results: 42 pts entered the study, M/F ratio: 27/15, median age: 59 (41-71), median WHO PS: 1 (0-1), histology: squamous 45%, adenocarcinoma 38%, other 17%. 12 pts entered the phase I, the maximum tolerated dose was reached at D 40 mg/m 2, reversible oesophagitis was the dose limiting toxicity. 33 pts have been treated at the recommended dose of D 30 mg/m 2, 1 pt was ineligible (kidney metastasis). Among the 24 pts evaluable for response, an objective response rate (ORR) of 62.5% (95% CI: 40.6-81.2) was observed (8 CR, 7 PR) and confirmed by external expert review. At the recommended dose, the median survival time is 13.6 months (95% Ch 8.2-24.8), the one-year survival is 59.4% (95% CI: 40.6-76.3) and the median time to progression is 12 months (95% CI: 5.1-36.0). The median duration of response (ORR) is 104.6 wks (95% CI: 52.0156.3). The median follow-up period is 9 months (95% Ch 3.3-33.2). 122 cycles were administered (median = 4, range 1-4). The median relative dose intensity was 100%. All pts (N = 33) were evaluable for safety. No grade 3-4 hematological toxicity was observed. Nonhematological side effects: 78% of pts experienced mild to moderate dysphagia, grade 3-4:1 infection, 1 stomatitis, 1 myocardial infarction (recovered), 1 dyspnea, 1 nausea and 1 neuropathy were observed. Conclusion: Docetaxel 30 mg/m 2 weekly for 4 weeks with concurrent radiotherapy (50 Gy) is effective and well tolerated. The simplicity of this chemoradiation regimen facilitates its use for standard stage Ill NSCLC chemotherapy na'~'vepts radiation treatment routines. A phase III randomized comparative trial is ongoing.
Thursday, 14 S e p t e m b e r 2000
8:30-10:00
ORAL SESSION
Combined
•2-•
Modality Therapy
Outcome results of long term follow up, for population based cohort of patients with stage Ilia NSCLC treated with aggressive combined modality treatment approach in a prospective study
S El-Sayed, A Leylek, M Akra, C. Mihalcioiu. University of Manitoba, Winnipeg, Canada
Introduction: Lung cancer is the leading cause of cancer deaths worldwide, historically Radiotherapy was the standard treatment for locally advanced NSCLC producing 5 years disease free survival of around 5%. Recent studies have shown that AGGRESSIVE COMBINED MODALITY treatment is superior to radiotherapy alone in prolonging survival. Objectives: To evaluate the feasibility and potential value of concomitant radiation and chemotherapy followed with surgery in improving the outcome of patients with stage IliA NSCLC in a prospective study setting. The primary end point of the study is Toxicity of the combined modality treatment. Methods: ELIGIBILITY: Patients selected for the study were deemed to have stage IliA, histologically confirmed NSCLC. performance status (KPS) of = or >70%, acceptable pulmonary and renal functions, and signed informed consent. TREATMENT REGIMEN: Treatment included Radiotherapy of 5000 cgy/20 F, days 1-28 in case of small volume or 3500 cgy/10 F, days 1-14 in case of large volume, combined with concomitant chemotherapy with cisplatinum 50 mg/m2 IVI day 1-5, 21-25. Results: From July 1991 to November 1995, 30 patients were accrued with age range of 40-71 years and average age of 59 years. Histology: 14 patients with adenocarcinoma, 8 with squamous cell carcinoma and 8 with poorly differentiated tumors. The majority of the patients presented with cough and dyspnea, some were asymptomatic at presentation. Most of the patients received the planned chemo/radiotherapy. While 9 patients had radical surgery (Iobectomy or pneumonectomy). Toxicity While all patients have required hospitalization for the 5 days of concomitant chemo-radiation, overall, the toxicity of the treatment was mild with no treatment-related death or delay in radiotherapy treatments. SURVIVAL Out of the 30 patients 28 died of their disease and 2 lost to follow up after 15 and 25 months. The median survival is 16 months. Conclusions: The treatment protocol is practical and feasible. The treated patients were more advanced than the average. No doubt that aggressive combined modality treatment prolong survival but distant metastasis remains the main cause of treatment failure. Long term disease free survival remains poor. It is possible that more aggressive chemo/radiotherapy schedules could produce better results. ~ - 9 - ] Early whole brain concomitant radiotherapy-chemotherapy for non-small cell lung cancer (NSCLC) brain metastases. A phase 2 study C. Ngo Quy 1, M.-A. Hailer 1, A. Darut-Jouve 2, G. Jolimoy2, D. Spa~th 3, V. Beckendorf3, T. Bazarbachi 1, E. Luporsi 3, B. Coudert 2, Y. Martinet 1. I Fed6ration de Pneumologie, H6pital de Brabois, Nancy; 2Service d'Oncologie Medicale, Centre Anticancereux G.F. Leclerc, Dijon; 3 Centre Anticancereux A. Vautrin, Vandoeuvre-les-Nancy, France Brain is a frequent secondary location in NSCLC. The combination of chemotherapy (CT) and radiotherapy could increase treatment efficiency by interfering with the cell ability to repair the specific injuries induced by each treatment.
Combined Modafi~ Therapy We have evaluated in an open, non-randomized, prospective, multicenter study, the toxicity and the efficiency of concomitant whole brain radiotherapy (WBRT) (3 Gy x 10 fractions during the first CT cycle) and CT [cisplatin 100 mg/m 2 day (d) 1, oral etoposide 50-100 mg/d (dl to d14), 3 21 d cycles] in NSCLC brain metastases. Toxicity and neurological function were rated according to the WHO criteria and the Order scale. Efficiency was assessed by CT Scan after 3 CT cycles. Patients (pts) were followed every 3 months. Sixteen pts were included, 3 were non evaluable (2 refusals after the consent, 1 accidental loss of patient's file), 13 evaluable: 11 men, 2 women; median age 54 y; 8 adenocarcinoma, 2 squamous cell carcinoma, 2 undifferenciated, 1 large cell carcinoma. At the brain level, 7 objective responses (3 complete), 4 stabilisations and 2 progression were observed. The global response was: 3 partial responses, 7 stabilisations and 3 progressions. The toxicity was: neutropenia: 2 pts grade 3, 5 pts grade 4 (4 sepsis); nausea: 2 pts grade 3, 1 pt grade 4; alopecia: 10 pts grade 3; hearing loss: 2 pts; intracranial hypertension increased in 3 pts during WBRT but was controlled by medical treatment in 2 pts. Neurological function was improved in 4 pts, stable in 6, and worsened in 3. In sept. 99, 9 pts were dead (4 pts died of brain progression and 5 pts died of thoracic progression) with a median survival (MS) of 40.1 weeks (w) (range: 4.3-78.9 w), without brain progression of 26.3 w (range: 0-59.6 w), and without disease progression of 16.1 w (range: 0-34.1 w); 4 pts are still alive, with a median follow-up of 40.6 w (range: 37.7-47.3 w), a MS without brain progression of 39.5 w (range: 25.7-47.3 w), and without disease progression of 31.4 w (range: 21.6-47.3 w). These results show an acceptable toxicity, an encouraging brain objective response rate and survival, and justify to carry on the study.
[-3-~ Brain metastases of lung cancer: Long-term results after concurrent chemoradiotherapy with cisplatin-etoposide F. Reboul, ¥. Brewer, P Vincent, B. Chauvet, C.F. Felix Faure, M. Taulelle. Lung Unit, Institut Sainte Catherine, Avignon, France Brain metastases (BM) are a major problem in patients (pts) with lung cancer, especially when local control has been achieved after combined modality therapy. Results of whole brain radiation therapy (WBRT) are unsatifactory with an average expected survival of 4 months. Chemotherapy (CT) with cisplatin-etoposide (PE) is active against BM with response rates of 20-30%. PE also shows radiosensitizing properties when administered concurrently with radiation. We hypothesized that concurrent WBRT + PE could improve local brain tumor control over WBRT alone in patients with inoperable BM. Methods: Treatment consisted of WBRT (36 Gy in 15 fractions over 3 weeks) with concurrent PE administered once during the 2 nd week of WBRT (P 20 mg/m2/d + E 50 mg/m2/d for 5 days). No additional CT was given after this 3-week treatment. Results: From 01/94 to 04/98, 78 consecutive pts were propectively treated according to this regimen. Characteristics: median age 63.8 years, sex-ratio 6.8, WHO status 2-3 57.7%, adenocarcinoma 41% Median BM diameter was 20 mm with 52.5% multiple BM. Median time from the diagnosis of lung cancer was 7.2 mo with 73% occuring within the first 12 mo. Toxicity was mild, with less than 10% Grade 3-4 adverse events, except universal alopecia. Complete radiological response was observed in 28 pts (36%). With a median follow-up of 46.8 mo, median survival was 7 mo with an overall survival at 1, 2 3 and 4 years of 24.4%, 12%, 10% and 10%, respectively. Definitive control of BM was observed in 73% of pts. Median survival was significantly better (p < .0001) in patients with WHO status 0-1 (11.4 mo), local control of the primary tumor (11.2 mo), complete radiologic response (14.3 mo) and a disease-free interval > 12 months (20.6 mo). After multivariate analysis, WHO status and disease-free interval > 12 mo were the only significant factors for long-term survival (32.6% at 4 years). There was no significant neuro-cognitive impairment in longterm survivors. Conclusions: Combined WBRT + concurrent PE significantly improves control of BM with an encouraging proportion of long-term survivors and should be compared in a randomized trial with WBRT alone or combined with radiosurgery.
101
I - ~ ~ Sequential chemotherapy and radiotherapy in non-small cell lung cancer LF.L Gaspar, RM.C. Susano, M Ortiz, E. Teixeira, R. Sotto-Mayor.
Santa Maria University Hospital, Lisbon; Elvas Hospital, Elves, Portugal Purpose: To evaluate median survival overall survival local progression-free survival and distant progression-free survival. Materials and Methods: One hundred patients with stage III nonsmall cell lung cancer (NSCLC) and Karnofsky Index > 70 were treated from 1992 to 1998 with a sequential approach of chemotherapy (CT) and radiotherapy (RT). 90 male and 10 female; median age = 64.5 years (range 38-77); 24 in stage IliA and 76 in stage IIIB; 46 squamous cell carcinomas, 34 adenocarcinomas, 3 mixed turnouts, 16 unclassified NSCLC and 1 large cell carcinoma. 3 or 4 cycles of CT were performed, 23 patients with mitomicin + vindesine + cisplatin (MVP), 58 with mitomicin + ifosfamide + cisplatin (MIP), 14 with vinorelbine + ifosfamide + cisplatin (NIP) and 5 with gemcitabine + cisplatin (GP); CT was followed by RT in conventional fractionation, 60 Gy/6 weeks; 8 patients underwent a total dose < 60 Gy due to poor performance status and/or disease progression. Results: Median survival = 17 months without statistic significance according to histology: 17 months in squamous cell carcinomas and 14 months in adenocarcinomas (p = 0.6), according to stage: 23 months in IliA and 16 months in IIIB (p = 0.16), according to type of CT: 18 months with MVP, 17 months with MIP, 15 months with NIP and 10 months with GP (p = 0.79) and according to RT dose: 17 months with 60 Gy and 9 months with <60 Gy (p = 0.069). Overall survival at 1 and 2 years is 69.2% and 36% respectively and survival probability at 3 and 5 years is 23.3% and 11.6% respectively. Median time to local progression is 15 months and local progression-free survival at 1, 2 and 3 years is 65.9%, 28.7% and 26.7% respectively. Median time to distant progression is 17 months and distant progression-free survival at 1, 2 and 3 years is 58.8%, 38.2% and 34.2% respectively; brain is the most frequent site of dissemination (37%), followed by bone (33.3%), lung (16.6%) and liver (13%). Overall survival results according to stage, histology and type of CT will also be presented. Conclusion: These results are similar to those published in randomized studies. Distant progression is more likely to occur during the first year and local progression is more frequent during the second year. At this time, there are no differences between CT schemes, although the recent ones (NIP and GP) include few patients. A concomitant approach of CT and RT with an acceptable toxicity might achieve better results in NSCLC.
•3-•
Carboplatinlpaclitaxel (C/P) or carboplatinlvinorelbine (CN) followed by accelerated hyperfractionated conformal radiation therapy (AHCRT): A phase I dose esclation trial from the Carolina conformal therapy consortium
L.B. Marks, MA. Socinski, J. Garst, G.S. Sibley, W. Blackstock, A. Turrisi, J. Herndon, S. Zhou, M Anscher, J. Crawford, J. Rosenman. Duke University, Durham, North Carolina; UNC Chapel
Hill, Chapel Hill, North Carolina, USA Combined modality therapy is the standard of care for patients (pts) with unresectable stage III NSCLC. The optimal radiotherapeutic strategy is not known. Conformal planning techniques allow enhanced tumor targeting and the possibility of delivering higher doses with acceptable toxicity. This trial is designed to assess the maximum tolerated dose (MTD) of AHCRT at 1.6 Gy BID following either induction C/P or C N for unresectable IIB-IIIB NSCLC. The initial dose of AHCRT was 73.6 Gy planned conformally (PLUNC: Plan Univ. of North Carolina). Regional lymph nodes received a minimum of 1.25 Gy BID to 45 Gy. All areas of gross disease received 1.6 Gy BID. Patients were enrolled in groups of 14, with AHCRT doses escalated in 6.4 Gy intervals (73.6 Gy, 80 Gy, 86.4 Gy and 92.8 Gy), Within each cohort, 7 received induction C/P and 7 received induction CN. The C/P and C N cohorts were considered separately so as to evaluate the impact of the induction regimen on the rate of grade 3 toxicity, and thus the