CANCER DU POUMON A PETITES CELLULES: EXPERIENCE DU NATIONAL CANCER INSTITUTE (USA)

J. D. Minna, P. A. Bunn, D. N. Carney, M. H. Cohen, F. Cuttita, B. E. Fosieck, A. F. Gazdar, D. C. Ihde, A. Johnston-Early, M. J. Matthews, R. Makuch, H. Oie, S. Rosen, A. Lichter, E. Glatstein

Research output: Contribution to journalArticle

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Abstract

This retrospective study deals with 168 patients with small-cell lung cancer (SCLC) who were treated at the NCI between March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 percent of all patients were disease-free far more than 40 months (25% of the limited disease and 3% of the external stage disease patients which were treated). Complete remission was essential to prolonged survival. The development of a complete remission was formed by a satisfactory initial general condition, localised disease, or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may include a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This led the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal-cord block above 2,000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are now underway using intensive chemotherapy with multiple-tumor site irradiation and autologous marrow inplants. 48 percent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease, whereas only 40 percent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. In spite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI: (1) Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of the APUD system and are secreted by SCLC. Bombesine has been isolated in all of the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. (2) These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. (3) In-vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). (4) Lastly, monoclonal AC has been prepared. In spite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.

Original languageEnglish (US)
Pages (from-to)83-93
Number of pages11
JournalBulletin du Cancer
Volume69
Issue number1
StatePublished - 1982

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National Cancer Institute (U.S.)
Neoplasms
Small Cell Lung Carcinoma
Drug Therapy
Radiotherapy
Thoracic Diseases
Lomustine
Procarbazine
Chromosomes, Human, Pair 14
Ifosfamide
Cachexia
Survival
Anorexia
Vincristine
Etoposide
Methotrexate
Cyclophosphamide
Disease-Free Survival
Arginine
Spinal Cord

ASJC Scopus subject areas

  • Oncology

Cite this

Minna, J. D., Bunn, P. A., Carney, D. N., Cohen, M. H., Cuttita, F., Fosieck, B. E., ... Glatstein, E. (1982). CANCER DU POUMON A PETITES CELLULES: EXPERIENCE DU NATIONAL CANCER INSTITUTE (USA). Bulletin du Cancer, 69(1), 83-93.

CANCER DU POUMON A PETITES CELLULES : EXPERIENCE DU NATIONAL CANCER INSTITUTE (USA). / Minna, J. D.; Bunn, P. A.; Carney, D. N.; Cohen, M. H.; Cuttita, F.; Fosieck, B. E.; Gazdar, A. F.; Ihde, D. C.; Johnston-Early, A.; Matthews, M. J.; Makuch, R.; Oie, H.; Rosen, S.; Lichter, A.; Glatstein, E.

In: Bulletin du Cancer, Vol. 69, No. 1, 1982, p. 83-93.

Research output: Contribution to journalArticle

Minna, JD, Bunn, PA, Carney, DN, Cohen, MH, Cuttita, F, Fosieck, BE, Gazdar, AF, Ihde, DC, Johnston-Early, A, Matthews, MJ, Makuch, R, Oie, H, Rosen, S, Lichter, A & Glatstein, E 1982, 'CANCER DU POUMON A PETITES CELLULES: EXPERIENCE DU NATIONAL CANCER INSTITUTE (USA)', Bulletin du Cancer, vol. 69, no. 1, pp. 83-93.
Minna JD, Bunn PA, Carney DN, Cohen MH, Cuttita F, Fosieck BE et al. CANCER DU POUMON A PETITES CELLULES: EXPERIENCE DU NATIONAL CANCER INSTITUTE (USA). Bulletin du Cancer. 1982;69(1):83-93.
Minna, J. D. ; Bunn, P. A. ; Carney, D. N. ; Cohen, M. H. ; Cuttita, F. ; Fosieck, B. E. ; Gazdar, A. F. ; Ihde, D. C. ; Johnston-Early, A. ; Matthews, M. J. ; Makuch, R. ; Oie, H. ; Rosen, S. ; Lichter, A. ; Glatstein, E. / CANCER DU POUMON A PETITES CELLULES : EXPERIENCE DU NATIONAL CANCER INSTITUTE (USA). In: Bulletin du Cancer. 1982 ; Vol. 69, No. 1. pp. 83-93.
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AU - Bunn, P. A.

AU - Carney, D. N.

AU - Cohen, M. H.

AU - Cuttita, F.

AU - Fosieck, B. E.

AU - Gazdar, A. F.

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AU - Matthews, M. J.

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N2 - This retrospective study deals with 168 patients with small-cell lung cancer (SCLC) who were treated at the NCI between March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 percent of all patients were disease-free far more than 40 months (25% of the limited disease and 3% of the external stage disease patients which were treated). Complete remission was essential to prolonged survival. The development of a complete remission was formed by a satisfactory initial general condition, localised disease, or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may include a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This led the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal-cord block above 2,000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are now underway using intensive chemotherapy with multiple-tumor site irradiation and autologous marrow inplants. 48 percent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease, whereas only 40 percent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. In spite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI: (1) Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of the APUD system and are secreted by SCLC. Bombesine has been isolated in all of the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. (2) These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. (3) In-vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). (4) Lastly, monoclonal AC has been prepared. In spite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.

AB - This retrospective study deals with 168 patients with small-cell lung cancer (SCLC) who were treated at the NCI between March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 percent of all patients were disease-free far more than 40 months (25% of the limited disease and 3% of the external stage disease patients which were treated). Complete remission was essential to prolonged survival. The development of a complete remission was formed by a satisfactory initial general condition, localised disease, or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may include a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This led the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal-cord block above 2,000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are now underway using intensive chemotherapy with multiple-tumor site irradiation and autologous marrow inplants. 48 percent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease, whereas only 40 percent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. In spite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI: (1) Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of the APUD system and are secreted by SCLC. Bombesine has been isolated in all of the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. (2) These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. (3) In-vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). (4) Lastly, monoclonal AC has been prepared. In spite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.

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