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Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide (ADOC) in invasive thymomas: Results in six patients
Annals of Oncology 4: 429-431, 1993. O 1993 Kluwer Academic Publishers. Primed in the Netherlands.
Short report Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide (ADOC) in invasive thymomas: Results in six patients A. Berruti, P. Borasio,1 A. Roncari, G. Gorzegno, C. Mossetti1 & L. Dogliotti Department of Clinical and Biological Sciences, University of Torino; ' Division of Thoracic Surgery, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy Summary
tine (0.6 mg/sqm) on day 2, and cyclophosphamide (700 mg/ sqm) on day 3, every 21 days - were administered to 5 Background: Locally advanced malignant thymomas are patients, while 1 patient received 5 cycles. usually radically resectable in about 60% of stage III but Results: 5/6 patients (83.3%) attained partial responses hardly ever in stage IVA. Neoadjuvant chemotherapy fol- and underwent radical surgery followed by two further lowed by surgery could improve both resection rate and ADOC cycles. The disease-free intervals were 5+, 6+, 15+, curability. Cisplatin containing regimens have repeatedly 16+, 26+ months. One patient showing stable disease at the been found to be highly active in advanced disease, with end of the fifth cycle was referred to radiotherapy. Toxicity overall response rates ranging from 80%-90%. was tolerable: grade III (WHO) nausea/vomiting and leukoPatients and methods: 3 patients with stage III and 3 with penia grade III occurred in 2 patients each. stage IVA invasive thymomas, according to Masaoka staging, Conclusions: These results suggest that the ADOC entered the study. Histology was: lymphoepithelial 4 cases, scheme is active as a neoadjuvant approach in invasive thyepithelial 2 cases. 4 cycles of the ADOC scheme - Adria- moma stages III and IVA, rendering possible radical resectmycin (40 mg/sqm), cisplatin (50 mg/sqm) on day 1, vincris- ability in 83% of patients.
Introduction
Materials and methods
Surgery and/or radiation therapy are widely accepted as being the standard primary treatments for invasive thymoma [1]. Their therapeutic indexes however, are often limited by either local involvement of unresectable structures or tumor dissemination outside the radiation fields [2j. As a consequence, most patients have local relapse and die of their disease |2). Systemic chemotherapy is usually reserved for patients with unresectable disease or who show progression after surgical or radiation therapy. Cisplatin-containing regimens have repeatedly been found highly active in patients with advanced disease, with overall response rates ranging from 80%-90% (3-5|. Fornasiero et al. [5] have recently published their single-institution experience with 37 patients with invasive thymoma who were uniformly treated with the ADOC scheme (cisplatin, adriamycin, vincristine and cyclophosphamide), achieving an overall response rate of 91.8%. These encouraging results prompted us to start a phase II study of the ADOC regimen in a neoadjuvant setting followed by surgery in patients with invasive thymoma. The present study reports the results obtained in the first six patients.
From February 1990 to June 1992 six patients (4 males and 2 females) with stages III—IVA invasive thymoma entered the study. The clinical characteristics of the patients are listed in Table 1. All patients were both chemotherapy- and radiotherapy-naive. Eligibility criteria included: histologic proof of thymoma; age less than 75 years, no history of malignancy other than basal cell carcinoma of the skin or in situ cervical cancer; measurable disease; performance status of 0 to 3 according to the ECOG scale; adequate bone marrow reserve (leukocyte count > 3.500/microL, platelet count > 100.000/microL)and liver (bilirubin < 1.5 mg/dl)and renal (serum crealinine < 1.5 mg/dl, creatinine clearance > 65 ml/min) function. The pretreatment staging procedures included history and physical examination, chest radiogram, screening chemistries, CT scan of the chest and abdomen, and mediastinoscopy with mediastinal resection biopsy. Thymomas were classified according to the predominant cell Table I. Patient characteristics. Initials
Sex
R.P. C.R. G.C. P.S.
F M
A.B. S.M.
F M M M
Age
28 29 67 68 23 70
Histology
Stage
E LE LE LE E
IVA III III IVA III IVA
LE
Re-
sponse
PR PR PR
PR PR SD
SurDuration vival (months) 15+ 26+ 5+ 6+ 16+ -
18+
31 + 9+
1 1+ 20+ 14+
PR: partial remission; SD: stable disease; LE: lymphoepithelial, E: epithelial.
430
IV [11]. Thus, neoadjuvant chemotherapy is highly justified in this stage of the disease. Combination chemotherapy is an effective treatment modality. Because thymoma is a relatively rare neoplasm, several schemes have been employed but only small series of patients per study have been involved. Overall, cisplatin-containing regimens seemed to be superior to non-platinum-containing ones, even though such superiority has not been supported by comparative studies, due to the rarity of the disease. The ADOC scheme has been employed in a single-institution series of 37 patients [5], 34 of them responders (91.8%). The activity of the ADOC scheme as neoadjuvant chemotherapy was recently convincingly proposed by Fornasiero et al. [12) and is confirmed in this study. Five of six patients (83.3%) with stages III and IVA attained PR and were treated with radical surgery. Toxicity was acceptable. A different selection of patients Partial response (PR) was defined as a 50% or greater reduction could account for the absence of complete responders in the sum of the products of the largest diameter and its perpenin our series, in contrast to the 30% of CR in Fornadicular, as compared with the lowest value recorded. Toxicity was reported according to the WHO criteria [8]. All pa- siero's [12]. One patient (PR.), a 28-year-old female tients with clinical complete or partial responses underwent surgery. with stage IV lympho-epithelial thymoma is notable for Resection was defined as radical if all macroscopic disease was re- her presentation with the unusual finding of amenormoved, and all surgical margins were free of tumor. Patients with rhea with high gonadotrophin serum levels, undetectmalignant cells at postoperative histology received two further ADOC cycles. Radiotherapy was planned only in patients with no able levels of ovarian steroids, and steathorrea due to a non-alcoholic exocrine pancreas insufficiency lasting response or incomplete surgical debulking. one year after thymoma detection. Both symptoms dramatically improved after the complete resection of thymoma, with resumption of menstrual cycles. A comResults mon autoimmune mechanism, even if speculative, could not be excluded, considering that autoimmune All patients received 4 cycles of ADOC except for one mechanisms have been reported in the pathogenesis of with stable disease who received 5 cycles. Five of six patients (83.3%) attained clinical PR. Radical surgery chronic pancreatitis 113]. was performed with evidence of malignant residual disTo conclude, these preliminary data suggest that ease at post-surgery histology. The disease-free inter- neoadjuvant ADOC chemotherapy + surgery is an vals were 5+, 6+, 15+, 16+, and 26+ months, and over- effective multidisciplinary treatment for patients with all survivals are 9+, 11+, 18+, 20+ and 31+ months. invasive thymoma which is presumably non-radically One patient with a stage IVA lymphoepithelial malig- resectable. nant thymoma who showed stable disease at the end of The usefulness of adjuvant radiotherapy in patients the fifth cycle was referred to radiotherapy. Fourteen with no evidence of disease is a matter of debate requirmonths after diagnosis, he is still alive, and has had ing multi-institutional prospective randomized studies. stable disease for 9+ months. Toxicity was tolerable, as previously reported [5|. Grade II |8] leukopenia occurred in 3 patients and grade III in 2 patients. Non- References hematological toxicity was mild, including alopecia 1. Maggi G, Giaccone G, Donadio M et al. Thymomas: A review grade III in all patients, nausea and vomiting grade II in of 169 cases with particular reference to results of surgical 3 patients and grade III in 2 patients, and grade II oral treatment. Cancer 1986; 58: 765-76. mucositis in 1 patient. type: a) lymphocytic, b) epithelial, c) mixed lympho-epithelial. Stage was assessed according to the Masaoka classification |7| as follows: I, macroscopically completely encapsulated; II, microscopic invasion into capsule and/or macroscopic invasion into surrounding fatty tissue, mediastinal pleura, and both; III, macroscopic invasion into contiguous visceral structures; IVA pleural or pericardial dissemination; IVB lymphogenous or hematogenous metastases. No patients showed myasthenia gravis, lupus erythematosus, pure red aplasia or hypogammaglobulinemia. One patient showed amenorrhea in association with steatorrhea, lasting one year prior to the thymoma detection. All patients were treated with the combination of adriamycin (40 mg/sqm) and cisplatin (50 mg/sqm) on day one; vincristine (0.6 mg/sqm) on day two and cyclophosphamide (700 mg/sqm) on day four (ADOC). This scheme was repeated every three weeks. First evaluation was performed after two courses with chest radiography and blood chemistry. Complete restaging, including computed tomography of the chest and upper abdomen, was done after 4 cycles. Response criteria were assessed in accordance with WHO |8|, and in particular, complete remission (CR) was defined as complete disappearance of all clinical, radiological, and biochemical evidence of disease for a minimum of 1 month.
Discussion Surgery remains the treatment of choice for invasive thymoma. Radical resection, however, is feasible in 100% of stage I—11 patients, but only in around 60% of stage III, and hardly ever in stage IVA, as recently reported |9|. The risk of late recurrence, as reviewed by Wilkins et al. [10), is significantly higher in stage III patients than stage I—II ones and identical to that in stage
2. Uematsu M, Kondo M. A proposal for treatment of invasive thymoma. Cancer 1986; 58: 1979-84. 3. Hu E, Levine J. Chemotherapy of malignant thymoma. Cancer 1986; 57: 1101-4. 4. Loehrer PJ, Perez C, Roth IM et al. Cisplatin plus adriamycin plus cyclophosphamide in limited and extensive thymoma: Preliminary results of an intergroup trial. Proc Am Soc Clin Oncol 1988; 7: 199. 5. Fornasiero A, Daniele O, Ghiotto C et al. Chemotherapy for invasive thymoma. A 13-year experience. Cancer 1991; 68: 30-3. 6. Macchiarini P, Chella A, Ducci F et al. Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 1991; 68: 706-13.
431 Masaoka A, Monden Y, Nakahara K et al. Follow-up study of thymoma with reference to their clinical stages. Cancer 1981; 48:2485-92. WHO handbook for reporting results of cancer treatment. Geneva, World Health Organisation, 1979 (offset publication No. 48). Maggi G, Casadio C, Cavallo A et al. Thymoma: results of 241 operated cases. Ann ThoracSurg 1991; 51: 152-6. 10. Wilkins EW, Grillo HC, Scannel GJ et al. Role of staging in prognosis and management of thymoma. Ann Thorac Surg 1991; 51: 888-92. Pescarmona E, Rendina EA, Venuta F et al. Analysis of prognostic factors and clinicopathological staging of thymoma. Ann ThoracSurg 1990; 50: 534-8. 12. Fornasiero A, Daniele O, Ghiotto C et al. Neoadjuvant treat-
Book review Immunodeficient mice in oncology. H. H. Fiebig, D. P.
Berger (eds). Karger Verlag, Basel/Miinchen/Paris/ London/New York/New Delhi/Bangkok/Singapore/ Tokyo/Sydney, 1992. 600 pp, III., US$132.00, £71.80, DM 198.00, Sfr. 165.00. This book assembles contributions to an international symposium on 'Immunodeficient mice in Oncology' held in November 1990 in Freiburg, Germany. Immunodeficient mice have been an invaluable tool in oncology since the first transplant of a human tumor in a thymusless nude mouse in 1969. The book is divided into four parts: the first is on the establishment of human tumor lines in nude mice, the second on their exploitation for studies in tumor biology, the third on mice with severe combined immunodeficiency (SCID), and the fourth on the use of these models for evaluation of treatment protocols. It is unfortunate that the
ment in locally advanced thymoma. Third International Congress on Neoadjuvant Chemotherapy: 1991; 90 Paris, France. 13. Bedossa P, Bacci J, Lemaigre G, Martin E. Lymphocyte subsets and HLA-DR expression in normal pancreas and chronic pancreatitis. Pancreas 1990; 5:415-20. Received 9 December 1992; accepted 20 January 1993. Correspondence to: Prof. Luigi Dogliotti, M.D. Oncologia Medica Ospedale S. Luigi Gonzaga Regione Gonzole 10 10043 Orbassano, Italy
Annals of Oncology 4: 431, 1993.
contributions are not divided into four corresponding parts in the table of contents listing. The book provides an overview of the field, as seen mostly from a European perspective. Contributions are heterogeneous in quality of size, and there is a certain amount of overlap, as is inevitable in a conference proceedings book. Some one-page chapters are in fact abstracts and should not have been included. The short chapters dilute the more thorough, systematic contributions. Among the ones this reviewer found of particular interest are those on the use of immunodeficient mice for preclinical drug testing. All in all, the book offers a useful overview of the field as of 1990. A. Mantovani Milan
Short report Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide (ADOC) in invasive thymomas: Results in six patients A. Berruti, P. Borasio,1 A. Roncari, G. Gorzegno, C. Mossetti1 & L. Dogliotti Department of Clinical and Biological Sciences, University of Torino; ' Division of Thoracic Surgery, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy Summary
tine (0.6 mg/sqm) on day 2, and cyclophosphamide (700 mg/ sqm) on day 3, every 21 days - were administered to 5 Background: Locally advanced malignant thymomas are patients, while 1 patient received 5 cycles. usually radically resectable in about 60% of stage III but Results: 5/6 patients (83.3%) attained partial responses hardly ever in stage IVA. Neoadjuvant chemotherapy fol- and underwent radical surgery followed by two further lowed by surgery could improve both resection rate and ADOC cycles. The disease-free intervals were 5+, 6+, 15+, curability. Cisplatin containing regimens have repeatedly 16+, 26+ months. One patient showing stable disease at the been found to be highly active in advanced disease, with end of the fifth cycle was referred to radiotherapy. Toxicity overall response rates ranging from 80%-90%. was tolerable: grade III (WHO) nausea/vomiting and leukoPatients and methods: 3 patients with stage III and 3 with penia grade III occurred in 2 patients each. stage IVA invasive thymomas, according to Masaoka staging, Conclusions: These results suggest that the ADOC entered the study. Histology was: lymphoepithelial 4 cases, scheme is active as a neoadjuvant approach in invasive thyepithelial 2 cases. 4 cycles of the ADOC scheme - Adria- moma stages III and IVA, rendering possible radical resectmycin (40 mg/sqm), cisplatin (50 mg/sqm) on day 1, vincris- ability in 83% of patients.
Introduction
Materials and methods
Surgery and/or radiation therapy are widely accepted as being the standard primary treatments for invasive thymoma [1]. Their therapeutic indexes however, are often limited by either local involvement of unresectable structures or tumor dissemination outside the radiation fields [2j. As a consequence, most patients have local relapse and die of their disease |2). Systemic chemotherapy is usually reserved for patients with unresectable disease or who show progression after surgical or radiation therapy. Cisplatin-containing regimens have repeatedly been found highly active in patients with advanced disease, with overall response rates ranging from 80%-90% (3-5|. Fornasiero et al. [5] have recently published their single-institution experience with 37 patients with invasive thymoma who were uniformly treated with the ADOC scheme (cisplatin, adriamycin, vincristine and cyclophosphamide), achieving an overall response rate of 91.8%. These encouraging results prompted us to start a phase II study of the ADOC regimen in a neoadjuvant setting followed by surgery in patients with invasive thymoma. The present study reports the results obtained in the first six patients.
From February 1990 to June 1992 six patients (4 males and 2 females) with stages III—IVA invasive thymoma entered the study. The clinical characteristics of the patients are listed in Table 1. All patients were both chemotherapy- and radiotherapy-naive. Eligibility criteria included: histologic proof of thymoma; age less than 75 years, no history of malignancy other than basal cell carcinoma of the skin or in situ cervical cancer; measurable disease; performance status of 0 to 3 according to the ECOG scale; adequate bone marrow reserve (leukocyte count > 3.500/microL, platelet count > 100.000/microL)and liver (bilirubin < 1.5 mg/dl)and renal (serum crealinine < 1.5 mg/dl, creatinine clearance > 65 ml/min) function. The pretreatment staging procedures included history and physical examination, chest radiogram, screening chemistries, CT scan of the chest and abdomen, and mediastinoscopy with mediastinal resection biopsy. Thymomas were classified according to the predominant cell Table I. Patient characteristics. Initials
Sex
R.P. C.R. G.C. P.S.
F M
A.B. S.M.
F M M M
Age
28 29 67 68 23 70
Histology
Stage
E LE LE LE E
IVA III III IVA III IVA
LE
Re-
sponse
PR PR PR
PR PR SD
SurDuration vival (months) 15+ 26+ 5+ 6+ 16+ -
18+
31 + 9+
1 1+ 20+ 14+
PR: partial remission; SD: stable disease; LE: lymphoepithelial, E: epithelial.
430
IV [11]. Thus, neoadjuvant chemotherapy is highly justified in this stage of the disease. Combination chemotherapy is an effective treatment modality. Because thymoma is a relatively rare neoplasm, several schemes have been employed but only small series of patients per study have been involved. Overall, cisplatin-containing regimens seemed to be superior to non-platinum-containing ones, even though such superiority has not been supported by comparative studies, due to the rarity of the disease. The ADOC scheme has been employed in a single-institution series of 37 patients [5], 34 of them responders (91.8%). The activity of the ADOC scheme as neoadjuvant chemotherapy was recently convincingly proposed by Fornasiero et al. [12) and is confirmed in this study. Five of six patients (83.3%) with stages III and IVA attained PR and were treated with radical surgery. Toxicity was acceptable. A different selection of patients Partial response (PR) was defined as a 50% or greater reduction could account for the absence of complete responders in the sum of the products of the largest diameter and its perpenin our series, in contrast to the 30% of CR in Fornadicular, as compared with the lowest value recorded. Toxicity was reported according to the WHO criteria [8]. All pa- siero's [12]. One patient (PR.), a 28-year-old female tients with clinical complete or partial responses underwent surgery. with stage IV lympho-epithelial thymoma is notable for Resection was defined as radical if all macroscopic disease was re- her presentation with the unusual finding of amenormoved, and all surgical margins were free of tumor. Patients with rhea with high gonadotrophin serum levels, undetectmalignant cells at postoperative histology received two further ADOC cycles. Radiotherapy was planned only in patients with no able levels of ovarian steroids, and steathorrea due to a non-alcoholic exocrine pancreas insufficiency lasting response or incomplete surgical debulking. one year after thymoma detection. Both symptoms dramatically improved after the complete resection of thymoma, with resumption of menstrual cycles. A comResults mon autoimmune mechanism, even if speculative, could not be excluded, considering that autoimmune All patients received 4 cycles of ADOC except for one mechanisms have been reported in the pathogenesis of with stable disease who received 5 cycles. Five of six patients (83.3%) attained clinical PR. Radical surgery chronic pancreatitis 113]. was performed with evidence of malignant residual disTo conclude, these preliminary data suggest that ease at post-surgery histology. The disease-free inter- neoadjuvant ADOC chemotherapy + surgery is an vals were 5+, 6+, 15+, 16+, and 26+ months, and over- effective multidisciplinary treatment for patients with all survivals are 9+, 11+, 18+, 20+ and 31+ months. invasive thymoma which is presumably non-radically One patient with a stage IVA lymphoepithelial malig- resectable. nant thymoma who showed stable disease at the end of The usefulness of adjuvant radiotherapy in patients the fifth cycle was referred to radiotherapy. Fourteen with no evidence of disease is a matter of debate requirmonths after diagnosis, he is still alive, and has had ing multi-institutional prospective randomized studies. stable disease for 9+ months. Toxicity was tolerable, as previously reported [5|. Grade II |8] leukopenia occurred in 3 patients and grade III in 2 patients. Non- References hematological toxicity was mild, including alopecia 1. Maggi G, Giaccone G, Donadio M et al. Thymomas: A review grade III in all patients, nausea and vomiting grade II in of 169 cases with particular reference to results of surgical 3 patients and grade III in 2 patients, and grade II oral treatment. Cancer 1986; 58: 765-76. mucositis in 1 patient. type: a) lymphocytic, b) epithelial, c) mixed lympho-epithelial. Stage was assessed according to the Masaoka classification |7| as follows: I, macroscopically completely encapsulated; II, microscopic invasion into capsule and/or macroscopic invasion into surrounding fatty tissue, mediastinal pleura, and both; III, macroscopic invasion into contiguous visceral structures; IVA pleural or pericardial dissemination; IVB lymphogenous or hematogenous metastases. No patients showed myasthenia gravis, lupus erythematosus, pure red aplasia or hypogammaglobulinemia. One patient showed amenorrhea in association with steatorrhea, lasting one year prior to the thymoma detection. All patients were treated with the combination of adriamycin (40 mg/sqm) and cisplatin (50 mg/sqm) on day one; vincristine (0.6 mg/sqm) on day two and cyclophosphamide (700 mg/sqm) on day four (ADOC). This scheme was repeated every three weeks. First evaluation was performed after two courses with chest radiography and blood chemistry. Complete restaging, including computed tomography of the chest and upper abdomen, was done after 4 cycles. Response criteria were assessed in accordance with WHO |8|, and in particular, complete remission (CR) was defined as complete disappearance of all clinical, radiological, and biochemical evidence of disease for a minimum of 1 month.
Discussion Surgery remains the treatment of choice for invasive thymoma. Radical resection, however, is feasible in 100% of stage I—11 patients, but only in around 60% of stage III, and hardly ever in stage IVA, as recently reported |9|. The risk of late recurrence, as reviewed by Wilkins et al. [10), is significantly higher in stage III patients than stage I—II ones and identical to that in stage
2. Uematsu M, Kondo M. A proposal for treatment of invasive thymoma. Cancer 1986; 58: 1979-84. 3. Hu E, Levine J. Chemotherapy of malignant thymoma. Cancer 1986; 57: 1101-4. 4. Loehrer PJ, Perez C, Roth IM et al. Cisplatin plus adriamycin plus cyclophosphamide in limited and extensive thymoma: Preliminary results of an intergroup trial. Proc Am Soc Clin Oncol 1988; 7: 199. 5. Fornasiero A, Daniele O, Ghiotto C et al. Chemotherapy for invasive thymoma. A 13-year experience. Cancer 1991; 68: 30-3. 6. Macchiarini P, Chella A, Ducci F et al. Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 1991; 68: 706-13.
431 Masaoka A, Monden Y, Nakahara K et al. Follow-up study of thymoma with reference to their clinical stages. Cancer 1981; 48:2485-92. WHO handbook for reporting results of cancer treatment. Geneva, World Health Organisation, 1979 (offset publication No. 48). Maggi G, Casadio C, Cavallo A et al. Thymoma: results of 241 operated cases. Ann ThoracSurg 1991; 51: 152-6. 10. Wilkins EW, Grillo HC, Scannel GJ et al. Role of staging in prognosis and management of thymoma. Ann Thorac Surg 1991; 51: 888-92. Pescarmona E, Rendina EA, Venuta F et al. Analysis of prognostic factors and clinicopathological staging of thymoma. Ann ThoracSurg 1990; 50: 534-8. 12. Fornasiero A, Daniele O, Ghiotto C et al. Neoadjuvant treat-
Book review Immunodeficient mice in oncology. H. H. Fiebig, D. P.
Berger (eds). Karger Verlag, Basel/Miinchen/Paris/ London/New York/New Delhi/Bangkok/Singapore/ Tokyo/Sydney, 1992. 600 pp, III., US$132.00, £71.80, DM 198.00, Sfr. 165.00. This book assembles contributions to an international symposium on 'Immunodeficient mice in Oncology' held in November 1990 in Freiburg, Germany. Immunodeficient mice have been an invaluable tool in oncology since the first transplant of a human tumor in a thymusless nude mouse in 1969. The book is divided into four parts: the first is on the establishment of human tumor lines in nude mice, the second on their exploitation for studies in tumor biology, the third on mice with severe combined immunodeficiency (SCID), and the fourth on the use of these models for evaluation of treatment protocols. It is unfortunate that the
ment in locally advanced thymoma. Third International Congress on Neoadjuvant Chemotherapy: 1991; 90 Paris, France. 13. Bedossa P, Bacci J, Lemaigre G, Martin E. Lymphocyte subsets and HLA-DR expression in normal pancreas and chronic pancreatitis. Pancreas 1990; 5:415-20. Received 9 December 1992; accepted 20 January 1993. Correspondence to: Prof. Luigi Dogliotti, M.D. Oncologia Medica Ospedale S. Luigi Gonzaga Regione Gonzole 10 10043 Orbassano, Italy
Annals of Oncology 4: 431, 1993.
contributions are not divided into four corresponding parts in the table of contents listing. The book provides an overview of the field, as seen mostly from a European perspective. Contributions are heterogeneous in quality of size, and there is a certain amount of overlap, as is inevitable in a conference proceedings book. Some one-page chapters are in fact abstracts and should not have been included. The short chapters dilute the more thorough, systematic contributions. Among the ones this reviewer found of particular interest are those on the use of immunodeficient mice for preclinical drug testing. All in all, the book offers a useful overview of the field as of 1990. A. Mantovani Milan