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Cisplatin and etoposide for locally advanced or metastatic thymoma. A phase II study of the EORTC lung cancer cooperative group
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Increased chemotherapy dosage with rG-CSF support versus standard dose chemotherapy in NSCLC J. v. Paw& U. Gatzemeler. N. Macha, N. Nlederie, W. Hlddemann, M. Nowrouskin. E. Groclen, lh. l+scht Dept. of Oncology, Hospitals of Munich, Hamburg, Hemer. Leverkusen. Monster. Essen and Amgen GmbH. Munich. Germany
4’epidoxorubicin (Epi DX) in elderly or unfit patients (pts) with small cell lung cancer (SCLC): a phase II experience by the EORTC Lung Cancer Cooperative Group E.QUOIX, H.KARNICKA, J.JASSEM, E. WIATR, H.CORTES TEN G.J.M. FUNES, K.ROOZENDAAL, VELDE, A.KIRKPATRICK, N.VAN ZANDWIJK Between July 1985 and April 1989, 41 previously untreated SCLC pts received Epi DX in a 3 weekly schedule (110 mg)/mZ i.v.) .Characteris’cics of the pts: median age 74 (range 53-84), median performance status 2(range O-31, male/female ratio 7: 1. Fifteen pts presented with limited, 23 pts with extensive disease. A total of 172 courses was administered to 40 DX patients with a median dose of 436 mg/m2 Epi (range 82-998) 8 pts were (partly) inevaluable (refusal 2, protocol violations 2, insufficient measurements 4j.33 pts were evaluable for response: 3 CR (9%), 16 PR (48%) and 6 non responders. There were 8 early deaths, 4 due to malignant disease, 2 toxic deaths and 2 due to apparently unrelated causes. Median duration of response was 5.7 months (range 2.2-15). Hematological toxicity was assessed in 32 pts (50% with leukocytopenia grade 3, 6% with thrombopenia grade 3, 3% with anemia grade 3. Non hematological side effects consisted of alopecia, nausea, stomatitis, diarrhea. Cardiological problems (ejection fraction 60%) were seen in 8% of the pts. In conclusion, Epi DX at a dose of 110 mg/m2 q 3 wks is an effective single agent in elderly or unfit SCLC pts. Considering the group of pts included the toxicity was judged as acceptable.
To evaluate the role of Increased dose comblnatlon chemotherapy in the treatment of llmited and exterelve stage NSCLC with regard to response rate and tlme to progression. we performed a prospective randomked phase Ill trial compurlng standard wlih Increased dose of carboplatln/vlndeslne. To avoid increased myelotozdcliy rG-CSF was added to the increased dose of chemotherapy. Dose and schedule: Treatment A: Vlndeslne 2.5 mg/m2, day 1 and 3. carboplatin 300mg/m2 , day 2. Treatment B: Vlndeslne 3 day 1 and 3. carboplatin 400 mg/2, day 2: rG-CSF mglm2, @q/kg/day). day 4 to 17 for up to 6 cycles. Resuk Between Oct. 90 and May 91,78 pis. entered the ongoing protocol. At this time. 39 pts. received 1 to 6 courses and were evaluable for response and toxlclty. Characteristics of pts. were almost identical In both groups IA: 19 pis. B: 20 pts). Response: Treatment A: CR/PR 0. NC 16. PD 3. Treatment B: CR/PR 4. NC 16. Five early death due to tumor progression were seen In treatment group A compared to 1 In group 8. Toxlclty: Nausea/Vomiting (WHO I-III) was the most common side effect of chemotherapy, and was equal In severlly and lncldence In both groups. Mild to moderate bone pain was the only rG-CSF related side effect. Conclusion: Higher dose Inter&y chemotherapy with rG-CSF suppoft seems to be superior to lower dose treatment.
506 CISPLATIN AND ETOPOSIDE FOR LOCALLY ADVANCED OR METASTATIC THYMOMA. A PHASE II STUDY OF THE EORTC LUNG CANCER COOPERATIVE GROUP. N.van Zandwijk, A.Kirkpatrick, G.Giaccone, A.Ardizzoni, for the EORTC LU"g Cancer .J.G.McVie O.Dalesio, Cooperative Group. Since September 1985, 15 patients with locally advanced or metastatic thymoma have been entered in a multicentre phase II study of cisplatin 60 mg/m* day 1, and etoposide 120 mg/m2 days 1,2,3, repeated every 3 weeks. Median age 9 were males, (range ZO-67), ECOG 43 years was performance status was O-l in 11, myasthenia gravis was in 1, present in 4, and prior surgery was radical subtotal in 9 and only a biopsy was taken in 3. Prior prior given in 2 and "one had radiotherapy was chemotherapy. Disease was predominantly mediastinal in 4, extramediastinal intrathoracic in 9 and extrathoracic predominantly lymphocytic, Histology was in 2. and 5 mixed in 4, 6, patients epithelial, or Patients received a median of 6 courses respectively. nausea/vomiting and alopecia (range Z-9). Leukopenia, were the most frequent side effects. Dose reduction or treatment delays were sometimes required, due to marrow toxicity. One patient died suddenly of acute cardiac failure and is not evaluable for response. Out of 14 patients evaluable for response 4 had complete response, 5 partial response and 5 no change. Median duration of and weeks, survival are 150 100 response and the combination of conclusion, respectively. In active combination etoposide is an and cisplatin chemotherapy in advanced thymoma. Its investigation in a neoadjuvant setting for inoperable cases is warranted.
RANDGMIZED TRIAL OF HIGH VS. STANDARD DOSE VP16/CISPLATIN IN EXTENSIVE SMALL CELL LUNG CANCER (SCLC). D. Ihde, J. Mulshine, B. Kramer, S. Steinberg, M. Edison, R. phelps, M. Le-sar. J. Pbarea, J. Minna. 8. Johnson. NCI-Navy Med. Gnc. Br., Natl. Cancer Inst., Natl. Naval Med. Center, and USUHS, Bethesda, MD 20814, U.S.A. Benefits of higher than usual doses of the commonly used VPl6hisplatin regimen in initial chemotherapy of SCLC are uncertain. We randomized previously untreated ambulatory pts with extensive SCLC and no major organ dysfunction to either VP16 80 mg/m* days l-3 + cisphtin SO mg/& day 1 (shndard dose) or VP16 80 mg/m2 + cisplatin 27 mglm’ days l-5 (67% higher dose) IV pts or those with qfwks for wks l-6 of therapy. N olumhlary organ dysfunction were given standard doses. All pts received stemlard doses in wks 7-12. In wks 13-24, pts received either VP16/cisplatin, vincristine/doxorubicin/cyclophosphamide, or a regimen based on in vih drug testing results. Tumor response improved in wks 13-24 in only 6 pts (I on high, 2 on standard dose). 108 pts are entered (83 randomized). Acti delivered doserate intensity during wka l-6 was 44% higher in the high compared to the standard dose arm. At 55 mos median follow-up. results are: Med Sun, CR/PR Nadir WBC/Plt N 12 mos 1.6Kl53K 40 2s%l60% fish 11 mos 2.5K/161K 43 21 %I6096 Stnndud 4%/68% 6nws 1.8K189K Nonrend 25 CR rates @=0X) and overall survival @=0.93) am almost identical in pts randomixed to high and standard doses. Chwyear survival is 52% for high and 47% for standard dose arms (95% confidence interval from 16% superiority for bigb to 7% for standard dose). We conclude 1) standard dose VPl6kisplatin is a very active regimen in extensive SCLC, despite only modest myelosuppressicm, and 2) there is no evidence of superior efficacy when drug doses are increased during the first 6 wks of therapy.
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Increased chemotherapy dosage with rG-CSF support versus standard dose chemotherapy in NSCLC J. v. Paw& U. Gatzemeler. N. Macha, N. Nlederie, W. Hlddemann, M. Nowrouskin. E. Groclen, lh. l+scht Dept. of Oncology, Hospitals of Munich, Hamburg, Hemer. Leverkusen. Monster. Essen and Amgen GmbH. Munich. Germany
4’epidoxorubicin (Epi DX) in elderly or unfit patients (pts) with small cell lung cancer (SCLC): a phase II experience by the EORTC Lung Cancer Cooperative Group E.QUOIX, H.KARNICKA, J.JASSEM, E. WIATR, H.CORTES TEN G.J.M. FUNES, K.ROOZENDAAL, VELDE, A.KIRKPATRICK, N.VAN ZANDWIJK Between July 1985 and April 1989, 41 previously untreated SCLC pts received Epi DX in a 3 weekly schedule (110 mg)/mZ i.v.) .Characteris’cics of the pts: median age 74 (range 53-84), median performance status 2(range O-31, male/female ratio 7: 1. Fifteen pts presented with limited, 23 pts with extensive disease. A total of 172 courses was administered to 40 DX patients with a median dose of 436 mg/m2 Epi (range 82-998) 8 pts were (partly) inevaluable (refusal 2, protocol violations 2, insufficient measurements 4j.33 pts were evaluable for response: 3 CR (9%), 16 PR (48%) and 6 non responders. There were 8 early deaths, 4 due to malignant disease, 2 toxic deaths and 2 due to apparently unrelated causes. Median duration of response was 5.7 months (range 2.2-15). Hematological toxicity was assessed in 32 pts (50% with leukocytopenia grade 3, 6% with thrombopenia grade 3, 3% with anemia grade 3. Non hematological side effects consisted of alopecia, nausea, stomatitis, diarrhea. Cardiological problems (ejection fraction 60%) were seen in 8% of the pts. In conclusion, Epi DX at a dose of 110 mg/m2 q 3 wks is an effective single agent in elderly or unfit SCLC pts. Considering the group of pts included the toxicity was judged as acceptable.
To evaluate the role of Increased dose comblnatlon chemotherapy in the treatment of llmited and exterelve stage NSCLC with regard to response rate and tlme to progression. we performed a prospective randomked phase Ill trial compurlng standard wlih Increased dose of carboplatln/vlndeslne. To avoid increased myelotozdcliy rG-CSF was added to the increased dose of chemotherapy. Dose and schedule: Treatment A: Vlndeslne 2.5 mg/m2, day 1 and 3. carboplatin 300mg/m2 , day 2. Treatment B: Vlndeslne 3 day 1 and 3. carboplatin 400 mg/2, day 2: rG-CSF mglm2, @q/kg/day). day 4 to 17 for up to 6 cycles. Resuk Between Oct. 90 and May 91,78 pis. entered the ongoing protocol. At this time. 39 pts. received 1 to 6 courses and were evaluable for response and toxlclty. Characteristics of pts. were almost identical In both groups IA: 19 pis. B: 20 pts). Response: Treatment A: CR/PR 0. NC 16. PD 3. Treatment B: CR/PR 4. NC 16. Five early death due to tumor progression were seen In treatment group A compared to 1 In group 8. Toxlclty: Nausea/Vomiting (WHO I-III) was the most common side effect of chemotherapy, and was equal In severlly and lncldence In both groups. Mild to moderate bone pain was the only rG-CSF related side effect. Conclusion: Higher dose Inter&y chemotherapy with rG-CSF suppoft seems to be superior to lower dose treatment.
506 CISPLATIN AND ETOPOSIDE FOR LOCALLY ADVANCED OR METASTATIC THYMOMA. A PHASE II STUDY OF THE EORTC LUNG CANCER COOPERATIVE GROUP. N.van Zandwijk, A.Kirkpatrick, G.Giaccone, A.Ardizzoni, for the EORTC LU"g Cancer .J.G.McVie O.Dalesio, Cooperative Group. Since September 1985, 15 patients with locally advanced or metastatic thymoma have been entered in a multicentre phase II study of cisplatin 60 mg/m* day 1, and etoposide 120 mg/m2 days 1,2,3, repeated every 3 weeks. Median age 9 were males, (range ZO-67), ECOG 43 years was performance status was O-l in 11, myasthenia gravis was in 1, present in 4, and prior surgery was radical subtotal in 9 and only a biopsy was taken in 3. Prior prior given in 2 and "one had radiotherapy was chemotherapy. Disease was predominantly mediastinal in 4, extramediastinal intrathoracic in 9 and extrathoracic predominantly lymphocytic, Histology was in 2. and 5 mixed in 4, 6, patients epithelial, or Patients received a median of 6 courses respectively. nausea/vomiting and alopecia (range Z-9). Leukopenia, were the most frequent side effects. Dose reduction or treatment delays were sometimes required, due to marrow toxicity. One patient died suddenly of acute cardiac failure and is not evaluable for response. Out of 14 patients evaluable for response 4 had complete response, 5 partial response and 5 no change. Median duration of and weeks, survival are 150 100 response and the combination of conclusion, respectively. In active combination etoposide is an and cisplatin chemotherapy in advanced thymoma. Its investigation in a neoadjuvant setting for inoperable cases is warranted.
RANDGMIZED TRIAL OF HIGH VS. STANDARD DOSE VP16/CISPLATIN IN EXTENSIVE SMALL CELL LUNG CANCER (SCLC). D. Ihde, J. Mulshine, B. Kramer, S. Steinberg, M. Edison, R. phelps, M. Le-sar. J. Pbarea, J. Minna. 8. Johnson. NCI-Navy Med. Gnc. Br., Natl. Cancer Inst., Natl. Naval Med. Center, and USUHS, Bethesda, MD 20814, U.S.A. Benefits of higher than usual doses of the commonly used VPl6hisplatin regimen in initial chemotherapy of SCLC are uncertain. We randomized previously untreated ambulatory pts with extensive SCLC and no major organ dysfunction to either VP16 80 mg/m* days l-3 + cisphtin SO mg/& day 1 (shndard dose) or VP16 80 mg/m2 + cisplatin 27 mglm’ days l-5 (67% higher dose) IV pts or those with qfwks for wks l-6 of therapy. N olumhlary organ dysfunction were given standard doses. All pts received stemlard doses in wks 7-12. In wks 13-24, pts received either VP16/cisplatin, vincristine/doxorubicin/cyclophosphamide, or a regimen based on in vih drug testing results. Tumor response improved in wks 13-24 in only 6 pts (I on high, 2 on standard dose). 108 pts are entered (83 randomized). Acti delivered doserate intensity during wka l-6 was 44% higher in the high compared to the standard dose arm. At 55 mos median follow-up. results are: Med Sun, CR/PR Nadir WBC/Plt N 12 mos 1.6Kl53K 40 2s%l60% fish 11 mos 2.5K/161K 43 21 %I6096 Stnndud 4%/68% 6nws 1.8K189K Nonrend 25 CR rates @=0X) and overall survival @=0.93) am almost identical in pts randomixed to high and standard doses. Chwyear survival is 52% for high and 47% for standard dose arms (95% confidence interval from 16% superiority for bigb to 7% for standard dose). We conclude 1) standard dose VPl6kisplatin is a very active regimen in extensive SCLC, despite only modest myelosuppressicm, and 2) there is no evidence of superior efficacy when drug doses are increased during the first 6 wks of therapy.