Introduction Of Chemotherapy Research Articles

Die historische Entwicklung der Tuberkulose seit Robert Kochs Entdeckung des Tuberkelbazillus 1882

Robert Koch's single-handed discovery of M. tuberculosis, one of the most gigantic scientific accomplishments of all times, provided the necessary foundation for subsequent investigative breakthroughs that have made it possible for experts to begin to contemplate the ultimate eradication of TB: the dreaded pestilence that for centuries was the greatest cause of death in the world. Further important milestones in the fight against TB were the discovery of X-rays, the development of BCG vaccination, the introduction of chemotherapy and chemoprophylaxis, and deciphering the genome of Mycobacterium tuberculosis. First of all, though, we must find a way to deal with the recent resurgence of the disease in the poor countries of sub-Saharan Africa, which is being fueled by another scourge, HIV/AIDS. And there is also the global problem of worsening anti-TB drug resistance. Eradication is conceivable and a worthy goal, but, I suspect, we will need to wait for another one or two additional "milestones" to help us along before the long-awaited nirvana can finally occur.

"Targeted Therapies" beim NSCLC – Gegenwart und Zukunft

During the last decades considerable progress has been made in the treatment of Non Small Cell Lung Cancer (NSCLC) especially resulting from the introduction of chemotherapy. Based on the results of basic-science, a new era of medical oncology has now been entered. Targets of pivotal importance for the development and perpetuation of malignant proliferation have been identified and pharmaceutical compounds against these structures have been developed ("Targeted Therapies"). The resulting broadening of the therapeutic armamentarium has already changed some of the treatment-guidelines. At the same time, a large number of new drugs has entered the stage of clinical development and every oncologist is confronted with a large amount of new data and the resulting difficulties to keep up to date. Accordingly, the aim of this review is to provide an update on the most important recent developments in the field of "Targeted Therapy" against NSCLC.

Capecitabine in advanced gastric cancer

Since the routine introduction of chemotherapy for advanced gastric cancer in the early 1990s, median survival for gastric cancer has improved from 3 months, with best supportive care alone, to > 11 months in recently reported Phase III trials of triplet chemotherapy. Capecitabine is an orally-active fluoropyrimidine, which is selectively metabolised to fluorouracil in tumour cells. The combinations of platinum compounds and capecitabine have been evaluated in two recent, large, Phase III trials demonstrating non-inferiority in efficacy compared with platinum plus continuous infusion fluorouracil. In view of the convenience and flexibility of patients in adjusting dosage when encountering toxicities, capecitabine is replacing continuous infusion fluorouracil as the backbone of combination chemotherapy in advanced gastric cancer patients. Future trials evaluating biologicals are now incorporating capecitabine combinations as control arms in both advanced disease and peri-operative settings in gastric cancer.

Diagnostic Dilemma of an Unusual Pelvic Mass in a Young Girl

Dysgerminoma of ovary is the most common germ cell tumor, accounting for 50% of all germ cell tumor cases. About 20% of cases are diagnosed during pregnancy, and 80% occur in women under 30. It is rare to find both ovaries to be involved in germ cell tumors. The prognosis of patients with malignant germ cell has improved significantly over the last two decades after the introduction of chemotherapy specially cisplatin. The only exceptions are stage 1, grade 1, immature teratoma and stage 1A dysgerminoima who are followed up after surgery without adjuvant chemotherapy. Normal ovarian functions and fertility can be retained in most patients by following the conservative surgery.

Solid tumors in childhood: risk-based management

Since the introduction of chemotherapy for the treatment of childhood leukemia more than 50 years ago, the results of childhood cancer have improved dramatically. The 5-year survival rate of disease, many of which were uniformly fatal in the prechemotherapy era, reached to more than 75%. This remarkable improvement in survival is a direct result of the incorporation of chemotherapeutics into treatment regimens that previously relied only on surgery or radiotherapy for the primary tumor. The multimodality approach, which integrates surgery and radiotherapy to control local disease with chemotherapy to eradicate systemic or metastatic disease, has become the standard approach to treating most childhood cancers. The overall improvement in outcomes in childhood solid tumors has been related to the development of multidisplinary cooperative studies that has permitted the development of well-designed tumor treatment protocols characterized by uniform staging criteria, sharing informations in pathologic classification, uniform methods for tumor markers, oncogenes, and other biologic and genetic factors. Important advances in the biologic study of cancer and its genetic basis led to a number of observations that impact directly on the management of childhood solid tumors. Identification of specific genes, oncogenes, tumor markers, and other biologic and pathologic factors plays an important role in both staging and clarifying the risk categorization of individual patients. Treatment of the patient is influenced by the recognition of specific risk factors. This knowledge has resulted in a change in the approach to care based not only on staging criteria, but also on risk-based management. This concept uses various risk factors of outcomes. Risk-based management allows for each patient to maximize survival, minimize long-term morbidity and improve the quality of life, especially for children's growth and development.

Outcome of children with posterior fossa medulloblastoma: a single institution experience over the decade 1994–2003

While the impact of radiotherapy in the management of medulloblastoma was recognised, the introduction of chemotherapy was investigated in clinical trials and shown to confer an additional advantage. We reviewed the outcome of a series of consecutive patients to assess the impact in a population-based clinical establishment. A series of 38 children treated for medulloblastoma at Birmingham Children's Hospital between 1994 and 2003 was analysed. The effect of surgery, radiotherapy, chemotherapy and metastasis on survival was analysed. The overall 5-year survival rate was 61.4% for the 36 patients who had resective surgery, while 2 patients had biopsy only and died within a few months. There was no operative mortality. The incidence of hydrocephalus needing permanent shunting was higher in the first 3 years of life (p = 0.007, chi-square). The 5-year survival rate of patients with total and sub-total excision of medulloblastoma was 61.1% and 61.8%, respectively. The 5-year survival rate of patients older than 3 years was 73.4% and for patients under 3 years was 36.3% (p = 0.007, log rank). Metastases at presentation did not influence survival. All deaths occurred in the first 32 months. The contribution of chemotherapy in the improvement of the overall survival appears more evident in children younger than 3 years or presenting with metastases. The absence of significant difference in survival between patients with total or sub-total excision of medulloblastoma supports the view that total excision of medulloblastoma can be avoided when the risk for potential intra-operative damage and consequent neurological deficits is high.

Elevated exhalation of hydrogen peroxide and circulating IL-18 in patients with pulmonary tuberculosis

Mycobacteria are the strong stimulators of respiratory burst, resulting in production of reactive oxygen species and nitrogen intermediates. The aim of our study was to assess the concentration of hydrogen peroxide (H(2)O(2)) in expired breath condensate (EBC) and the serum level of interleukin-18 (IL-18) in patients with active pulmonary tuberculosis (TB) before introduction of chemotherapy and after 2 months of treatment. Sixteen patients, current cigarette smokers, with advanced pulmonary TB were enrolled into the study. As a control served two groups: I group--16 asymptomatic cigarette smokers, II group--17 healthy never smoked subjects. The level of H(2)O(2) in EBC was significantly higher in patients with TB (1.3+/-0.7 microM) as compared to cigarette are healthy nonsmoker subjects (0.4+/-0.1 and 0.2+/-0.1 microM, respectively, P<0.05). Two months of treatment significantly decreased the level of H(2)O(2) exhalation in TB patients (0.5+/-0.3 microM) to the value that was not different from that in asymptomatic smokers but was still higher than in never smoked subjects. Serum concentration of IL-18 in TB patients was higher than that found in both control groups either before and after antituberculous treatment (P<0.05). Exhaled H(2)O(2) did not correlate with circulating IL-18 in TB patients before or after treatment. These results demonstrated the occurrence of oxidative stress in the airways of TB patients completely attenuating after 2 months of successful antituberculous treatment.

Current strategies of chemotherapy in osteosarcoma

Osteosarcoma, the most common type of primary malignant tumour that develops in bone, can be classified into several different sub-types. While the majority of osteosarcomas are highly malignant, there are some low-grade variants. Since the introduction of chemotherapy into the multi-modal treatment regimen of high-grade osteosarcoma, its prognosis has impressively improved, with long-term survival being achieved in two-thirds of all patients. This review summarises current chemotherapeutic treatment strategies in classical osteosarcoma and also addresses the indication for chemotherapy in more unusual types and variants. It emphasises the need for treatment in specialised centres and within prospective, multi-institutional trials, amongst which EURAMOS1 and EURO-B.O.S.S are currently active in many European countries.

Efficacy and influence of neoadjuvant epirubicin/vinorelbine chemotherapy (EN) on molecular markers in inflammatory breast cancer (IBC) and preliminary results of a randomized study testing as adjuvant chemotherapy the same EN-combination versus docetaxel (TXT)

886 Background: IBC is the most aggressive form of breast cancer. The introduction of chemotherapy(CT) in multimodality approach of IBC resulted in improved survival, with about 30% pts alive and p...

Choriocarcinoma presented as a vaginal tumor

Choriocarcinoma presented as a vaginal tumor

Osteosarcoma of the jaw: The Chaim Sheba Medical Center experience

Objective: The purpose of this article is to present 14 cases of osteosarcoma of the jaw treated at our medical center from 1989 to 1998. These cases are discussed in the light of a comprehensive review of 774 cases reported in the English literature over the past 3 decades. Differences between osteosarcoma of the jaws and osteosarcoma of the long bones are examined. Subjects and Methods: The patients ranged in age from 8 to 78 years, the mean age being 33 years. Each patient had a histopathologically established diagnosis of osteosarcoma of the jaw. Records were reviewed for epidemiologic data, treatment modalities, and survival. Results: Of the 14 patients, 6 (42%) had tumors in the mandible and 8 (58%) had tumors in the maxilla. Of the mandibular tumors, 5 occurred in the body of the mandible; all maxillary tumors originated in the alveolar ridge and involved the maxillary sinus. The chief complaint was an intraoral or extraoral painless swelling. Histopathologic types included chondroblastic, osteoblastic, fibroblastic, and malignant fibrous histiocytoma–like. Pathologic grade was determined to be high (3 or 4) in 13 cases and low (1) in only 1 mandibular case. All patients underwent surgical resection and immediate reconstruction. Adjuvant therapy included postoperative radiation (5 patients), postoperative chemotherapy (2 patients), and preoperative chemotherapy and postoperative radiation (1 patient). Conclusions: The results of the present study support the literature indicating that osteosarcoma of the jaw differs from osteosarcoma of the long bones in its biological behavior even though they have the same histologic appearance. Because of differences in tumor characteristics, the introduction of chemotherapy did not dramatically alter the prognosis of osteosarcoma of the jaw. Early diagnosis and radical surgery are the keys to high survival rates. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:445-51)

メルケル細胞癌の１例

A 63 year-old man with Merkel cell carcinoma is reported. He noticed an asymptomatic reddish macule on his left lower leg about 8 years previously. The lesion gradually enlarged to a nodule. As the nodule expanded rapidly during past 3 months, he visited our hospital. At his first visit, the lesion was seen as a 70×70mm, indurated reddish plaque accompanied with a dark reddish nodule of 47×45×18mm in size. Biopsy specimen revealed aggregation of atypical small tumor cells, that were immunohistochemically positive for CK20, chromogranine A, and NSE, supporting the diagnosis of Merkel cell carcinoma. We performed wide resection of the primary lesion along with left inguinal lymph node dissection. Inguinal lymph node metastases were confirmed histopathologically. Postoperatively, radiotherapy (50.4Gy XRT) was perfoemed. However, multiple metastases to the liver, pancreas, and distant lymph nodes and local reccurence developed. He was treated with CAV/PE alternating chemotheapy. The metast tic and recurrent lesions reduced, indicating effectiveness of this regimen. After 4 months from the introduction of chemotherapy, the lesions enlarged again. Other regimens of chemotherapy were performed, but he was died due to complication of DIC. [Skin Cancer (Japan) 2001; 16: 51-55]

Neuroendocrine Small Cell Carcinoma of the Uterine Cervix: What Disease? What Treatment? Report of Ten Cases and a Review of the Literature

Neuroendocrine small cell carcinoma of the uterine cervix (NESCCC) is an entity with very aggressive behaviour. The optimal initial therapeutic approach to this rare disease has not yet been clearly defined.We reviewed our experience of this disease over the past 10 years with regard to chemosensitivity. Since 1988, ten patients (mean age 33 years; range 24–47) have been diagnosed with NESCCC and treated in our institutions. Disease stage at presentation was IA (one), IB (five, two with lymph node involvement), IIB (one), IIIB (one), and IV (two). One patient had metastatic disease at presentation; three developed metastases during initial treatment. Eight patients underwent surgery and eight received radiation therapy. Six patients received pre- or postoperative cisplatinumvepeside (PE) combination chemotherapy, either alone or concurrently with radiation therapy. PE alone as primary chemotherapy led to disease stabilization in the two patients so treated; concurrent PE and radiation therapy resulted in a pathological complete response in one patient. Eight patients relapsed within 16 months and died of their disease within 29 months from the initial diagnosis. Two patients are alive with no evidence of disease at 13 and 53 months.Our series confirms the previously described very poor prognosis of NESCCC, despite initial aggressive multidisciplinary treatment. It may be that the introduction of chemotherapy, especially combined primary chemoradiotherapy, might allow patients to do a little better, although at the moment there is no good evidence one way or the other.

Percutaneous Needle Aspiration for Benign Mediastinal Masses

Percutaneous needle aspiration (PCNA) of mediastinal masses is an effective modality for the diagnosis of malignancies, especially for staging of lung cancer. Its usefulness in diagnosing benign condition has been poorly documented. This study reports the results of 65 patients with benign mediastinal masses who were subjected to PCNA after prior work-up (including bronchial needle aspiration or mediastinoscopy in most cases) was nondiagnostic. The lesions measured from 2.3 to 10.5 cm in the largest diameter, with a mean of 4.6 cm. The following lesions were present: thymoma, 3; lipoma, 6; cyst, 12; tuberculosis, 14; nonspecific inflammation, 7; sarcoid, 4; thyroid, 5; abscess, 3; neurinoma, 3; rheumatoid inflammation, 1; aortic aneurysm, 2; Castleman's tumor, 1; osteochondroma, 1; and 3 remained undiagnosed. The patients were 13 to 75 years of age, with a mean age of 44.8 years. Forty-four were female, and 21 were male. Most patients were asymptomatic (40) or with unspecific symptoms, such as malaise (18), substernal pain (16), low-grade fever (12), and cough (10). There were no false-positive aspirates for malignancy. In four patients, the cytologic diagnosis was false-negative. PCNA resulted in introduction of chemotherapy in 11 of 14 patients with tuberculosis. Six of 12 cysts disappeared after PCNA. Contemplated surgery was abandoned in 4 of 6 patients with fatty mass and in 3 of 5 patients with mediastinal thyroid. A small pneumothorax occurred in 7 patients. PCNA is of value in the diagnosis of benign mediastinal masses. The cytologic diagnosis is reliable. PCNA may obviate the need for invasive diagnostic procedures and may lead to adequate treatment of tuberculosis.

LOCALLY ADVANCED BREAST CANCER

The multidisciplinary management of patients with locally advanced breast cancer (LABC) has evolved over the last three decades. The introduction of chemotherapy (CT) and endocrine therapy in conjunction with surgery and radiation therapy (XRT) have changed the natural history of this disease. The authors discuss the role of the taxanes, novel endocrine therapy, and high-dose CT programs in the management of LABC. Indications for breast-conserving surgery are presented. The role of prognostic and predictive tumor markers in LABC is discussed.

Childhood medulloblastoma in Denmark 1960-1984. A population-based retrospective study.

Medulloblastoma is a common paediatric brain tumour, located in the cerebellum and in the IV ventricle, surpassed in frequency only by astrocytomas. 180 children below the age of 15 with a medulloblastoma of the posterior fossa were treated in Denmark in the 25-year period from 1960 to 1984 and followed up until the end of 1996, or until death. During the 25 years they accounted for 20% of all intracranial tumours in children in Denmark. All tumours were histologically verified. The mean annual incidence was 6.4x10(-6), decreasing slightly with a factor of 0.12x10(-6) per year. The male/female ratio was 2.1 - twice that of the background population of children (1.05). The 5-year survival rate following diagnosis, surgery and radiotherapy was 23%, and the 25-year survival rate was 16%. The 5-year survival rate was 8% in the first 5-year period of 1960-1964, increasing to 36% in the last period 1980-1984. Presumably the increase in survival depends on many factors, e.g. improved diagnostic methods and neuroanaesthesia, better operative technique (microscope), improvements in radiotherapy and the introduction of chemotherapy. The best predictive factors of a good prognosis were preoperative CSF shunting, radical tumour removal and complete radiotherapy, i.e. irradiation of the brain, tumour bed and spinal cord. The survival rate in the last five-year period was seven times higher than the survival rate found in a comparable Danish study from the years 1935-1959. Most of the children followed Collins law of risk index. The results of treatment in children with medulloblastoma remain unsatisfactory. Accordingly, participation in international prospective studies of multimodal treatment should be encouraged, possibly using chemotherapy prior to surgery.

Mathematical modeling of the interrelationship of CD4 lymphocyte count and viral load changes induced by the protease inhibitor indinavir.

While CD4 cell counts are widely used to predict disease progression in human immunodeficiency virus (HIV)-infected patients, they are poorly explanatory of the progression to AIDS or death after the introduction of chemotherapy. Changes in HIV load (as measured by RNA PCR) have been shown to be a much better predictor of the risk of disease progression. Since the interrelationship of these markers is of great clinical interest, we modeled the time-averaged return of CD4 cell count and change in viral load subsequent to therapy with the HIV protease inhibitor indinavir. We found that CD4 cell return was significantly related to both the baseline CD4 count (r2 = 0.86, P < 0.001) and the decline in HIV RNA PCR-determined viral load (also referred to in this work as the HIV RNA PCR decline) (r2 = 0.60, P < 0.01). Simultaneously modeling both influences in a linked nonlinear model (r2 = 0.93, P < 0.001) demonstrated that (i) the starting number of CD4 cells accounted for the majority of the change in CD4 cell return and (ii) the return of CD4 cells attributable to viral load decrease was 50% of maximal with only a decrease of approximately 0.2 log of HIV RNA as modeled from the first 12 weeks of therapy. Much greater viral inhibition beyond that necessary for maximal CD4 cell return is possible. Given that HIV RNA PCR decline is more strongly linked to ultimate clinical course in HIV disease, our findings indicate that CD4 return is potentially misleading as an indicator of antiviral effect, since it is determined more by the starting CD4 value than by viral load decline and since near-maximal changes occur with minimal antiviral effect.

Hansen's disease and nephropathy as its sequence

Nephropathy as the sequences of Hansen's disease before and after the introduction of chemotherapy was compared referring to the report by Hayashi in 1943 and the summary of the autopsy reports from 1978 to 1981 at National Hansen's disease hospital Zenseien. Unlike the high rates of tuberculosis as the cause of death before the introduction of chemotherapy (41.3%) those thereafter decreased to be negligible. On the other hand the comparison of the rates of nephropathy with the same way as that of tuberculosis was impossible since the description about nephropathy by Hayashi was not sufficient to characterize each nephropathy since he included arteriolitis, glomerulonephritis and interstitial nephritis together in the term of nephritis. Death rate due to nephritis among Hansen's disease patients according to Hayashi at that time was 21.2% which was twice as many comparing to that in the other cases. According to the report about the cases of Zenseien those reported to have glomerulonephritis was 37.3% though those were not necessarily listed as the cause of death. Also the nephropathy including fibrinoid angitis with occasional microaneurysmal dilatation of afferent arteries, glomerulitis, sclerosis and stricture of efferent arteries likewise ischemic acute tubular necrosis possibly as the result of these angiopathy seemed to be present. These vascular changes partially resemble to that of microscopic periarteritis nodosa but seems to be common in the smaller arteries. In conclusion, unlike the case of tuberculosis the rate of nephritis including glomerulitis, arteriolitis and interstitial nephritis as Hayashi used as his criteria does not seem to have decreased. Therefore, the critical analysis of the nephropathy especially of that relating to the arteriolitis should be done to obtain the knowledge to suppress its occurrence.

Is bladder conservation feasible? An Indian experience

With the introduction of chemotherapy in the treatment of muscle invasive bladder cancers, endeavors at improving disease-free survival/overall survival are ongoing. As high objective response rates were seen with MVAC/CMV regimens (M-methotrexate, V-vinblastine, A-adriamycin, C-cisplatin) organ conservation is being attempted. A phase II protocol was designed using MVAC as the initial therapy. Based on the response to two cycles all patients were evaluated and where possible the bladder was preserved. Twenty-nine patients completed the protocol and had a median follow-up of 24 months. Complete response (CR) was noted in 7/29 (24.1%) of patients, while 11/29 (38%) had partial response (PR) and 11/29 (38%) showed no response (NR). Bladder conservation was possible in 15/29 (51.7%) patients initially with the use of radiation therapy after the initial chemotherapy. Ten of these patients are presently alive with their bladders intact. Three patients died of distant disease, two with normal bladders and one with local relapse. Two of the other patients required salvage cystectomy and are alive and disease-free. All complete responders 7/7 (100%) and 5/11 (45%) partial responders could have their bladders conserved. Three of 11 partial responders who refused radiotherapy and 11/11 non-responders underwent radical cystectomy after initial chemotherapy. Subset analysis indicates that low stage and grade tumours had the highest likelihood of bladder preservation, and there was no difference in overall survival in the groups according to response criteria. As our study consists of a small number of selected patients, it would be improper to draw firm conclusions. However, it seems that initial chemotherapy selects out a subset of patients with a good prognosis and the chance for bladder conservation.

Present and future projects of the International Breast Cancer Study Group.

The International Breast Cancer Study Group (formerly the Ludwig Group) has conducted nine clinical trials since 1978 (see the Appendix for participants and authors). Biologic hypotheses related to the combined use of chemotherapy and endocrine therapy in women with operable breast cancer were tested. Questions of timing of chemotherapy with respect to tumor surgery and late introduction of chemotherapy were also evaluated. Ongoing and future trials continue in this tradition to investigate combinations of available endocrine therapies and cytotoxic agents.