Rapidly alternating radiotherapy and high dose cisplatin in stage III non-small cell lung cancer...
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RECENT ADVANCES IN THE PATHOLOGICAL DIAGNOSIS OF LUNG CANCER Yukio Shimosato National Cancer Center Hospital, Tokyo, Japan For small cell lung cancer (SCLC), monoclonal antibodies recognizing cluster 1 SCLC antigen/N-CAM can be utilized for distinction of SCLC from non-SCLC. One of them, NCC- LU-243, was produced in our laboratory. Although the antigen was labile in formalin solution, antigenicity was preserved by addition of 2% zinc sulfate to the formalin. Almost all pure SCLC cells were reactive with this anti- body, but SCLC with large cell component and a few non- SCLC were focally reactive. Non-SCLC with positive reac- tion may not be neuroendocrine tumors but tumors showing oncofetal changes, since the antigen was said to be expressed in fetal lung epithelial cells. NCC-LU-243 can also be used for cytology smears. For adenocarcinoma, subtyping not only by histologic type but also by cell type is desirable, but this cannot be done for every tumor. Therefore, confirmation of mucus- producing ability is a minimal requirement, since Clara cell and type II pneumocyte types do not produce mucin, whereas bronchial epithelial and gland types do so. In addition. the deoree of nuclear atvuia and oroliferative activity.should -be determined in order to bredict the outcome in affected patients. In this regard, nuclear DNA content measured by cytofluorometry and the frequency of DNA-svnthesizina or oroliferatino cells determined bv immu&histochemFstry'are OF greaf help. Monoclonal antibody PE 10, which recognizes a surfactant apoprotein, was reactive with more than half of all pulmonary adenocarcinomas, irrespective of cell type and deoree of differentiation. exceot for ooblet cell-tvoe adenocarcinoma, and was n&-reactive with mesothelibha and adenocarcinoma of other organs, except for a few thyroid carcinomas. Therefore, it is considered an excellent marker for pulmonary adenocarcinoma. BIOMABKRRS OF SMALL CELL LUNG CANCER FA Grew, DH Johnson, Vanderbilt University Medical Center, Nashville, TN. The search for a clinically useful biamarker for small cell lung cancer continues. This neoplasm produces a number of peptides, enzymes and other substanceswhich can be measured in the tumor as well as the plasma and/or CSF. The following markers have been evaluated including: ACTH, ADH, calcitonin, CEX, NSE, creatine kinase BB. neurophysins, chromogranin A, bombesin and several other miscellaneous substances. Unfortunately many of the products demonsrrate a heterogenity of expression and it is unlikely thnt any one of the markers will be used exclusively and successfully in small cell lung cancer. A panel of markers may be mire useful although there is no absolute data yet to support this clinically. The combinationof NSE, chromogranin A, creatine kinase BB and CEA may be a marker combinationwhich will be clinicallyuseful and this is currently being investigated. There are clues that pretreatmentCEA and creatine kinase BB levels may provide useful prognostic information. It is anticipatedthat continuedprogress and understanding of the biology of small cell cancer will lead to improved methods of tumor detection and therapy. RAPIDLY ALTERNATING RADIOTHERAPY AND HIGH DOSE CISPLATIN IN STAGE III NON-SMALL CELL LUNG CANCER (NSCLC): RESULTS OF A PHASE I-II STUDY DR Gandara, FH Valone, EA Perez, AB Deisseroth, M Roach, DK Ahn, T Phillips. Northern California oncology Group (NCOG) Alternating radiotherapy CRT) and chemotherapy increases tumor cure rates in some animal models with reduced normal tissue damage compared to sequential use of these modalities. TO test this concept in NSCLC, patients (pts) with predominantly stage IIIB disease were treated on a NCOG pilot study of alternating RT and high dose cisplatin. RT consisted of 6000 cGy delivered in three separate 10 day courses of-200 cGy/fraction/day during weeks l-and 2, 5 and 6. and 9 and 10. Cisolatin. 100 ma/m2 in 3% saline was given on weeks 3 and 4, 7 and 8, 11 and 12, and 15 and 16. Median age 59 (40-70), stage IIIA/IIIB: 6/22. Results are reported in 29 pts with > 1 year of follow up. The response rate in 28 eligible pts is 71% (20/28) with six complete responses and 14 partial responses. Feasibility of this approach is demonstrated by 25/28 pts completing RT and a median of 2.5 courses of chemotherapy administered. Median survival time MST is 25 months (range 2-48+ months). MST in Stage IIIB is 11.2 mos. One and two year survival rates are 61% (17/28) and 32% (g/28) respectively. and radiation-related Hematologic, renal, toxicities were significant but manageable. We conclude that rapid alternation of RT and a high dose intensity cisplatin regimen is feasible in stage III NSCLC, with a high response rate and acceptable toxicity. The long-term impact on local control and survival remains unclear, although survival data are encouraging in this poor prognosis population. Further studies of this concept are warranted. NEOADJUVI\NTCHEMOTHERAPY (CT)ANDRADIOTIIERAPY(RT) FOLLOWED BY SURGERY (S) IN STAGE HM NON-SMALL CELL LUNG CANCER (NSCLC): A PHASE II STUDY OF THE CANCER AND LEUKEMIA GROUP B: G. Strauss, D. Sherman, M. Goutsou, D. Malhisen, R. Carey,N. Choi,V. Rege, C.Modeas,K. Pmpert, M. Green: Cancer andLeukemia GroupB,Lebanon, N.H. Thisstudy wns designed BS B phase II study lo determine the feasibility and etlkacy of combined modality therapy employing concurrent CT and RT followed by S in stage III A NSCLC. Pretreatment evnluation included bmnchoscopy, chest and abdominal CT, bone scan, and careful mediaslinoseopic staging. Neoadjuvant lreolment consisted of concurrent CT and RT. Patients then underwent S, which was followed in turn by additional CT and RT. CT included cisplotin 100 mglmt days 1 & 29, Velben 3 mg/m2 d 1 & 3, and 29 & 31, end 5-FU 30 mglkgld by infusion d l-3, and 29-31. RT began on day 1 and included 3,000 cGy in 15 fmctions over 3 weeks. S occurred on day 55, and one more cycle of CT and another 3,000 cGy of RT began on day 85. Forty-one patients were entered onto this phase II study. There were 32 males and 9 females with B median age of 57 years. Median followup of surviving patients is 46 months (range 37-52 months). Ilislolow: 13 squmnous, 14 sdeno, 13 large cell, 1 mixed. Staging: 1 TlN2, 28 ?2N2, 4 T3N2.3 TJNl.5T3NO. Response to ire-op CT/RT was 0 CR, 26 ((59%) PR, 16 (39%) stable, 1 (2%) progression. 31 patients undement S, and 25 were resected (11 pneumonectomy, 14 lobeclomy) including 16 PR and 9 stable cases. In 4 of the 25 resection specimens, no viable tumor was present, while in 3 of the 6 unresectable patients, extensive biopsies revealed only necrotic tumor. The maximum response achieved employing all protocol treatment was 27 (65%) CR, 7 (17%) PR, 6 (15%) stable disease. and I (2%) pmgression. Toxicity was substantinl end primarily hematologic. There were 6 patients (15%) in whom treatment contributed to patient deaths, including 3 perioperative deaths and 3 chemotherapy-related toxic deaths. The Kaplan-Meier curve indicated o 1 year survival of 58% nod n median survival of 16.5 months. 11 patients (27%) currently remain free of disease. We conclude that there is a high rate of partial response associated with the neoodjuvont CT/RT, and lhot a high percentage of patients are ultimately rendered completely disease-free. Whether suwivnl is improved by this approach co” only be delermlned through randomized
Transcript of Rapidly alternating radiotherapy and high dose cisplatin in stage III non-small cell lung cancer...
RECENT ADVANCES IN THE PATHOLOGICAL DIAGNOSIS OF LUNG CANCER Yukio Shimosato National Cancer Center Hospital, Tokyo, Japan
For small cell lung cancer (SCLC), monoclonal antibodies recognizing cluster 1 SCLC antigen/N-CAM can be utilized for distinction of SCLC from non-SCLC. One of them, NCC- LU-243, was produced in our laboratory. Although the antigen was labile in formalin solution, antigenicity was preserved by addition of 2% zinc sulfate to the formalin. Almost all pure SCLC cells were reactive with this anti- body, but SCLC with large cell component and a few non- SCLC were focally reactive. Non-SCLC with positive reac- tion may not be neuroendocrine tumors but tumors showing oncofetal changes, since the antigen was said to be expressed in fetal lung epithelial cells. NCC-LU-243 can also be used for cytology smears. For adenocarcinoma, subtyping not only by histologic type but also by cell type is desirable, but this cannot be done for every tumor. Therefore, confirmation of mucus- producing ability is a minimal requirement, since Clara cell and type II pneumocyte types do not produce mucin, whereas bronchial epithelial and gland types do so. In addition. the deoree of nuclear atvuia and oroliferative activity.should -be determined in order to bredict the outcome in affected patients. In this regard, nuclear DNA content measured by cytofluorometry and the frequency of DNA-svnthesizina or oroliferatino cells determined bv immu&histochemFstry'are OF greaf help. Monoclonal antibody PE 10, which recognizes a surfactant apoprotein, was reactive with more than half of all pulmonary adenocarcinomas, irrespective of cell type and deoree of differentiation. exceot for ooblet cell-tvoe adenocarcinoma, and was n&-reactive with mesothelibha and adenocarcinoma of other organs, except for a few thyroid carcinomas. Therefore, it is considered an excellent marker for pulmonary adenocarcinoma.
BIOMABKRRS OF SMALL CELL LUNG CANCER FA Grew, DH Johnson, Vanderbilt University Medical Center, Nashville, TN.
The search for a clinically useful biamarker for small cell lung cancer continues. This neoplasm produces a number of peptides, enzymes and other substances which can be measured in the tumor as well as the plasma and/or CSF. The following markers have been evaluated including: ACTH, ADH, calcitonin, CEX, NSE, creatine kinase BB. neurophysins, chromogranin A, bombesin and several other miscellaneous substances. Unfortunately many of the products demonsrrate a heterogenity of expression and it is unlikely thnt any one of the markers will be used exclusively and successfully in small cell lung cancer. A panel of markers may be mire useful although there is no absolute data yet to support this clinically. The combination of NSE, chromogranin A, creatine kinase BB and CEA may be a marker combination which will be clinically useful and this is currently being investigated. There are clues that pretreatment CEA and creatine kinase BB levels may provide useful prognostic information. It is anticipated that continued progress and understanding of the biology of small cell cancer will lead to improved methods of tumor detection and therapy.
RAPIDLY ALTERNATING RADIOTHERAPY AND HIGH DOSE CISPLATIN IN STAGE III NON-SMALL CELL LUNG CANCER (NSCLC): RESULTS OF A PHASE I-II STUDY DR Gandara, FH Valone, EA Perez, AB Deisseroth, M Roach, DK Ahn, T Phillips. Northern California oncology Group (NCOG)
Alternating radiotherapy CRT) and chemotherapy increases tumor cure rates in some animal models with reduced normal tissue damage
compared to sequential use of these modalities. TO test this concept in NSCLC, patients (pts) with predominantly stage IIIB disease were treated on a NCOG pilot study of alternating RT and high dose cisplatin. RT consisted of 6000 cGy delivered in three separate 10 day courses of-200 cGy/fraction/day during weeks l-and 2, 5 and 6. and 9 and 10. Cisolatin. 100 ma/m2 in 3% saline was given on weeks 3 and 4, 7 and 8, 11 and 12, and 15 and 16. Median age 59 (40-70), stage IIIA/IIIB: 6/22. Results are reported in 29 pts with > 1 year of follow up. The response rate in 28 eligible pts is 71% (20/28) with six complete responses and 14 partial responses. Feasibility of this approach is demonstrated by 25/28 pts completing RT and a median of 2.5 courses of chemotherapy administered. Median survival time MST is 25 months (range 2-48+ months). MST in Stage IIIB is 11.2 mos. One and two year survival rates are 61% (17/28) and 32% (g/28) respectively. and radiation-related
Hematologic, renal, toxicities were
significant but manageable. We conclude that rapid alternation of RT
and a high dose intensity cisplatin regimen is feasible in stage III NSCLC, with a high response rate and acceptable toxicity. The long-term impact on local control and survival remains unclear, although survival data are encouraging in this poor prognosis population. Further studies of this concept are warranted.
NEOADJUVI\NTCHEMOTHERAPY (CT)ANDRADIOTIIERAPY(RT) FOLLOWED BY SURGERY (S) IN STAGE HM NON-SMALL CELL LUNG CANCER (NSCLC): A PHASE II STUDY OF THE CANCER AND LEUKEMIA GROUP B: G. Strauss, D. Sherman, M. Goutsou, D. Malhisen, R. Carey,N. Choi,V. Rege, C.Modeas,K. Pmpert, M. Green: Cancer and Leukemia Group B, Lebanon, N.H.
This study wns designed BS B phase II study lo determine the feasibility and etlkacy of combined modality therapy employing concurrent CT and RT followed by S in stage III A NSCLC. Pretreatment evnluation included bmnchoscopy, chest and abdominal CT, bone scan, and careful mediaslinoseopic staging. Neoadjuvant lreolment consisted of concurrent CT and RT. Patients then underwent S, which was followed in turn by additional CT and RT. CT included cisplotin 100 mglmt days 1 & 29, Velben 3 mg/m2 d 1 & 3, and 29 & 31, end 5-FU 30 mglkgld by infusion d l-3, and 29-31. RT began on day 1 and included 3,000 cGy in 15 fmctions over 3 weeks. S occurred on day 55, and one more cycle of CT and another 3,000 cGy of RT began on day 85.
Forty-one patients were entered onto this phase II study. There were 32 males and 9 females with B median age of 57 years. Median followup of surviving patients is 46 months (range 37-52 months). Ilislolow: 13 squmnous, 14 sdeno, 13 large cell, 1 mixed. Staging: 1 TlN2, 28 ?2N2, 4 T3N2.3 TJNl.5 T3NO.
Response to ire-op CT/RT was 0 CR, 26 ((59%) PR, 16 (39%) stable, 1 (2%) progression. 31 patients undement S, and 25 were resected (11 pneumonectomy, 14 lobeclomy) including 16 PR and 9 stable cases. In 4 of the 25 resection specimens, no viable tumor was present, while in 3 of the 6 unresectable patients, extensive biopsies revealed only necrotic tumor. The maximum response achieved employing all protocol treatment was 27 (65%) CR, 7 (17%) PR, 6 (15%) stable disease. and I (2%) pmgression. Toxicity was substantinl end primarily hematologic. There were 6 patients (15%) in whom treatment contributed to patient deaths, including 3 perioperative deaths and 3 chemotherapy-related toxic deaths. The Kaplan-Meier curve indicated o 1 year survival of 58% nod n median survival of 16.5 months. 11 patients (27%) currently remain free of disease.
We conclude that there is a high rate of partial response associated with the neoodjuvont CT/RT, and lhot a high percentage of patients are ultimately rendered completely disease-free. Whether suwivnl is improved by this approach co” only be delermlned through randomized
