Springer Uitgeverij, Houten, 2009, 280 pp. It is a great honor and pleasure to be invited to review the book of Professor Theo Wagener entitled ‘The History of Oncology’, published by Springer in 2009. Char [1.Char D.H. History of ocular oncology.Ophthalmology. 1996; 103: S96-S101Abstract PubMed Google Scholar], an American ophthalmologist, wrote in 1996 that “Those who do not remember history are doomed to repeat it” and Nutton [2.Nutton V. Ancient Medicine. Taylor and Francis Group, London2004: 1-17Google Scholar], a British professor of history of medicine, in 2004 said that “History is an art of forgetting as well of remembrance”. Although the history of mankind is a continuum of events between the past, the present and the future, the history of medicine is a continued evolution of scientific progress associated mainly with advances in other basic sciences such as biology, biochemistry, pharmacology, physics, etc. Professor Wagener’s book is the first systematic study on the history of oncology from ancient times to the present. The book is organized into 10 chapters, each composed as a separate unit that can be read independently. We found ‘Chapter 2’ one of the most important chapters since he refers to the occurrence of cancer in the antiquity and also elaborates ideas and theories about the nature of the disease. The first references to cancer have been recorded in three Egyptian papyri dating from 2650 to 1950 BC and the information they yield is quite interesting because they describe various cases of breast tumor together with a uterine carcinoma. It should be mentioned, however, that as of today, there are ∼50 cases of cancers reported on mummies diagnosed both radiologically and pathologically. The most common ones were bone sarcomas, nasopharyngeal or breast carcinomas [3.Nerlich A.G. Pohrbach H. Bachmeier B. Zink A. Malignant tumors in two ancient populations: an approach to historical tumor epidemiology.Oncol Rep. 2006; 16: 197-202PubMed Google Scholar]. But the field in antiquity was dominated by Greek physicians, most notably by Hippocrates (ca. 460–370 BC) and Galen (ca. 130–200 AD), who developed the black bile theory and took a more pragmatic or scientific stand in explaining health and disease. Hippocrates liberated diseases from religions and superstitions, described clinical signs and symptoms of the various tumors, connecting them to the black bile, named ‘cancer’ from the Greek word ‘carcinos’ (means crab) and moreover established ethical rules in medicine [4.Reiser S.J. What modern physicians can learn from Hippocrates.Cancer. 2003; 98: 1555-1558Crossref PubMed Scopus (8) Google Scholar]. As to the Roman period, Aurelius Cornelius Celsus (c.30 BC–38 AD) described the phenomenon of metastatic process and Claudius Galenus (129–199 AD) introduced the term ‘sarcoma’ from the Greek word ‘sarca’ (flesh) and maintained that those who belong to the ‘melancholic type’ are more prone to develop cancer [5.Galen Kuhn C.G. Opera omnia. Vol. XI, II, 12.1826: 139-141Google Scholar]. A short referral to the ancient Chinese medicine and its contribution to the classification of cancer is also given, but no information about ancient Indian medicine is provided [6.Cabanne F. Gerald-Marchant R. Destaing F. Geschichte des Kebses.Illustriette Geschichte der Medizin. Deel 8. 1983: 2849-2870Google Scholar]. The creation of universities in Italy and France and the study of sciences throughout the Renaissance period opened new perspectives in medicine. First, there were doubts voiced on the bile theory, then followed the discovery of lymph as a cause of malignancy (when it leaks out of the lymph ducts and goes to the lymph nodes, it contaminates the whole system), and this breakthrough allowed various theories and speculations as to the cause of cancer. It was thought that it was produced by the body (as a kind of cancer toxin situated in the genitals) and that the disease was more widespread in northern climates than in the south, where there was greater sexual activity. At any rate, during this period, they focused upon infectious agents (insects, contaminated water, poor sanitation), made observations on the various types of malignancies and began to study the problem of metastasis. Since medicine in Middle Ages was suppressed by the dogmas of the catholic church, no adequate medical information or advances are available until the 14th century Renaissance, characterized by the presence of dominant medical personalities such as Andreas Vesalius (1514–1564) in anatomy, William Harvey (1578–1657) in blood circulation, Gasparo Aselli (1581–1626) in lymphatic system or Paracelsus (1493–1541) who supported that cancer was due to an excess of mineral salts [7.Sakorafas G.H. Safioleas M. Breast cancer surgery: an historical narrative. Part I. From prehistoric times to Renaissance.Eur J Cancer Care (Engl). 2009; 18: 530-544Crossref PubMed Scopus (28) Google Scholar]. Real advances in our knowledge of cancer were made, however, in the second half of the 18th century with the gathering of clinical data and case histories (undertaken in Padua) and the use of the microscope, which enabled the study of cancerous tissue. During the 18th and 19th centuries, we have some major advances in cancer medicine. Basically, pathological anatomy has been developed with the invention of the microscope and with the presence of autopsy findings. Giovanni Battista Morgagni (1682–1771) from Padua, Marie-Francois Xavier Bichat (1771–1802) from France as well as Johannes Muller (1801–1858) and Rudolf Ludwig Karl Virchow (1821–1902) from Germany were the ‘fathers’ of cancer pathology. They were the first among others who described microscopically the appearance of malignant tumors, the tumor stroma, the pathways of metastases and the association of inflammation and cancer. Eventually, not only observations in humans but also experiments in animals implicated infectious, chemical or radiation agents with carcinogenesis. It is also interesting to point out that in 1740, Jean Godinot (1661–1749) built up the first cancer hospital in the world in Rheims, dedicated to the support of cancer patients [8.Ewing J. Neoplastic Diseases. W.B. Saunders Company, Philadelphia, PA1919Crossref Google Scholar]. ‘Chapter 4’ deals with the evolution of surgery in the treatment of malignant tumors. Surgery is still considered the oldest therapy for cancer. In this chapter, the author covers the development of surgery itself as well as of surgical oncology separately by tumor site. In addition, he provides historical data on the development of anesthesia and antisepsis. The first gastric resection for cancer of the stomach was carried out in France in 1879, the first surgical removal of the rectum was done in Germany in 1887, the first radical mastectomy in England in 1890, the first removal of a spinal tumor in England in 1887 and the first successful pneumonectomy for lung cancer in the United States in 1933. During the 19th and 20th centuries, surgical oncology flourished both in Europe and the United States [9.Ellis H. A History of Surgery.2nd edition. Cambridge University Press, Cambridge, UK2009Google Scholar]. In conjunction with preoperative and postoperative radiotherapy and/or chemotherapy, new therapeutic avenues have opened especially in the outcome of solid tumors. ‘Chapter 5’ elaborates the historical development of radiotherapy. The ‘cathode rays’ were discovered in 1869 by Hittorf, in 1895 Roentgen made the first X-ray photo and in 1896 Voigt in Germany irradiated the first patient with a cancer of the throat. The same period the first cases with breast, skin and gastric cancer were treated in various European centers. Eventually, the progress in radiotherapy technology and radiology was tremendous especially after the First World War. Cyclotron was invented in 1939, betatron in 1940, cobalt-60 unit in 1948 and brachytherapy and linear accelerator in 1953. Recent developments in the history of radiation treatment include radiotherapy, planning computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography–CT and functional MRI; intensity-modulated radiation therapy; 4D irradiation or the combination of radiotherapy with hyperthermia [10.Holsti L.R. Development of clinical radiotherapy since 1896.Acta Oncol. 1995; 34: 995-1003Crossref PubMed Scopus (16) Google Scholar, 11.Fletcher G.H. Regaud lecture perspectives on the history of radiotherapy.Radiother Oncol. 1988; 12 (iii–v, 253–271)Abstract Full Text PDF PubMed Scopus (31) Google Scholar]. In ‘Chapter 6’, the author describes the development of chemotherapy from antiquity until recently. Although he mentions in general that remedies for cancer were made from herbs, minerals or animal products, we believe it is worthwhile to bring up some examples from the Greek–Roman antiquity. For example, one of Hippocrates’s (460–370 BC) remedy was a mixture of momordica elaterium, cucumber honeycomb and water in juice form or intravaginal clyster from uterus cancer; Dioscurides of Anazarous (1st c.AD) used terebinth oil, frankincense, hedge mustard and honey in plasters for hidden cancers; Leonides of Alexandria (1st c.AD) used asses’ or women's milk, opium, hyssop, lead monoxide, frankincense, pork fat, fresh butter and rose oil in plasters for application on breast cancer; Galen of Pergamon (2nd c.AD) used an ointment for external cancers consisting of calcined shells of whelk, purple shell fish, oysters, sea urchin, crab, sour wine, honey, pork fat and Cadmean earth and Oreibasios of Pergamon (320–400 AD) applied plasters for early cancers with strychnon, winter cherry, hound's berry, thorn apple and zinc oxide [12.Karpozilos A. Pavlidis N. The treatment of cancer in Greek antiquity.Eur J Cancer. 2004; 40: 2033-2040Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar]. The major part of this chapter (almost 80%), however, refers to an extensive historical overview of modern chemotherapy starting immediately after the Second World War and ending at the decade of 2000. In this part, all recent achievements of chemotherapy are presented for both solid and hematological malignancies [13.De Vita Jr, V.T. Chu E. A history of cancer chemotherapy.Cancer Res. 2008; 68: 8643-8653Crossref PubMed Scopus (1083) Google Scholar]. The historical development of endocrine treatment is the scope of ‘Chapter 7’. This chapter starts with interesting clinical and epidemiological observations implicating hormones with the appearance of endocrine-related cancers, followed by a thorough reference to hormonal treatment in both females and males. ‘Chapters 8 and 9’ cover the historical progress of both targeted treatments and immunotherapy. Most of this information refers to quite recent data since both kinds of therapies are related to the advances of various basic sciences. Finally, in ‘Chapter 10’, several topics from the psycho-oncology field are discussed. Among them are the social stigma of cancer, the communication between doctor and patient or the issue of psychosocial support. There is no doubt thought that the development of psycho-oncology is part of the modern oncology practice since such organized services require expert supportive teams, better hospital settlements and advanced society structures. To list the breakthroughs and the discoveries made in the 19th and 20th centuries would be tedious if not superfluous. It would suffice to say that the book goes into detailed discussion of the advances made in surgery and anesthesia, the introduction of antisepsis and other related topics. Fascinating is also the section on the results gained from the first microscopic studies, as for instance, that the structure of cancerous growths does not differ from normal tissue (the first law of oncology) and that cancer cells grow out of undifferentiated cells interspersed between normal tissue (blastema), and the section devoted to cancer transplants from animal to animal and even to human—experiments that opened the way to techniques for growing tissue and cell cultures. To include in this review a few minor corrections and additions would not minimize the value of this splendid book at the least: regarding the Greek word carcinos, meaning both ‘cancer’ and ‘crab’, and whether Hippocrates first used the term or rather Paul of Aegina because in breast cancer the blood vessels look like the legs of a crab. In our opinion, the parenthood of the term should be attributed to Hippocrates even though no trace of the analogy is found in his writings. On the other hand, Paul of Aegina (ca. 680 AD) should be excluded from the discussion because his excerpt on the analogy ‘cancer–crab’ has been borrowed directly from Galen, [14.Galen. De methodo medendi libri XIV. In Kuhn CG (ed.), Opera omnia. Vol. X, Leipzig, Germany: 1828; 83, 14Google Scholar]. Next, the statement made to the effect that with the fall of the “Greek Empire, Rome took over the scientific knowledge of medicine” (page 11) strictly speaking is not correct—for one, there existed no Greek empire at the time or at an earlier period—and the same can be said for a similar pronouncement made a few pages later that after the fall of the Roman Empire the center of medical science moved to Byzantium (page 14). The surviving Greek medical texts written in late antiquity and in the early Christian centuries up to the Justinianic Age (6th c. AD) were not necessarily connected with imperial capitals but with schools and centers of learning in large cities, one of the most prestigious being, of course, Alexandria. And for that matter, the bulk of the Greek medical texts available to us today dates before Byzantium was made the new center of the Roman Empire. It is also not true that after Galen there was little progress in the treatment of cancer. Galen's continuators relied heavily upon his writings, but again there were exceptions and deserve to be mentioned not only Oreibasios of Pergamon (ca. 320–400 AD) but also Archigenes (cancer of the uterus) and Aetios of Amida [12.Karpozilos A. Pavlidis N. The treatment of cancer in Greek antiquity.Eur J Cancer. 2004; 40: 2033-2040Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar]. As to surgical undertakings during the Middle Ages, Byzantine texts record various cases of surgical treatment carried out in hospitals supported by either religious foundations or the State. And a last word regarding Arab medicine: the medical treatise of Abou Djàfar Ah'mad (10th c.), known as Viaticum peregrinantis (provisions for the traveler as it was rendered into the Greek translation), discussed amongst others the various kinds of skin growths and ailments. But unfortunately, this work is known to us only from partial editions of the Greek translation [15.Dugat G. Études sur le traité de médecine d' Abou Djàfar Ah'mad, intitulé: Zâd al-moçâfir, La provision du voyageur.Journal Assiatique. 1853; 1 (ser. V): 289-353Google Scholar]. We feel that the presented pioneering work of Professor Theo Wagener has been internationally acknowledged. This book is interesting to read and very informative. It is a unique book that covers entirely the history of cancer in mankind. Despite the fact that a huge number of books in history of medicine are available, such a specific book dealing with the diagnosis and treatment of cancer during the last 6000 years was lacking. The authors declare no conflict of interest.
This trial was conducted by the Hellenic Cooperative Oncology Group to improve the responses and survival in small cell lung cancer with a good prognosis, using a weekly intensive chemotherapy with alternated non-cross-resistant myelosuppressive agents. Patients were classified into two groups; group A consisted of those who received the initial designed regimen (29 patients), and group B consisted of those who received the more intensified regimen that increased by 25% the doses of carboplatin, epirubicin, and ifosfamide, and by 33% the doses of etoposide given on days 1, 2, and 3 with prophylactic granulocyte colony-stimulating factor support. Chemotherapy in group A consisted of carboplatin 150 mg/m2 in 250 ml of 5% dextrose in water as an 1-hour infusion on day 1, etoposide 75 mg/m2 in 250 ml normal saline as an 1-hour infusion on days 1 and 2 alternating with epirubicin 30 mg/m2 intravenous push on day 8, and ifosfamide 2 g/m2 in 500 ml 5% dextrose in water as a 2-hour infusion with mesna protection on day 8. Responding patients with limited disease were also treated with thoracic irradiation. Those who achieved complete response received prophylactic cranial radiotherapy. In group A, the overall response rate was 79.3%, with a 27.6% complete response rate, a median time to progression of 5.71 months, and a median survival of 8.3 months. For patients with limited disease, the response rate was 75%, with a 40% complete response rate, a median time to progression of 5.87 months, and a median survival of 10.98 months. The respective numbers for extensive disease were 89% (only partial responses), 4.82 months, and 5.67 months. The toxicity was mild and manageable. There were no dose reductions or treatment delays. In view of the excellent tolerability and the rather low efficacy of the initial regimen, we decided to administer the more intensified one with granulocyte colony-stimulating factor support. In Group B, the overall response rate was 91.8%, with a 45.9% complete response rate, a median time to progression of 7.05 months, and a median survival of 10.16 months. For limited disease, the response rate was 93%, with a 52% complete response rate, a median time to progression of 7.05 months, and a median survival of 10.49 months. The respective numbers for extensive disease were 88% (25% complete response), 6.82 months, and 9.02 months. The toxicity of this more intensified regimen was more severe but acceptable. Myelosuppression was the main toxicity. However, grade 3-4 febrile neutropenia requiring hospitalization occurred only in 6% of patients. The relative dose intensity was 91%, probably the result of the prophylactic use of granulocyte colony-stimulating factor. The differences in response rate, time to progression, and survival were not statistically significant between the two groups. There were statistically significant differences in the response rate (p = 0.019) and survival rate (p = 0.001) between limited disease and extensive disease only in group A. In conclusion, this weekly, alternated regimen, specifically the intensified regimen, appears to be very active and well tolerated in patient who have small cell lung cancer with a good prognosis. However, despite the high efficacy, this study failed to show any survival advantage as compared with that obtained with the standard treatment for small cell lung cancer.
