Immunoradioautography test for alpha-fetoprotein in the differential diagnosis of germinogenic tumours of the testis and in the evaluation of effectiveness of their treatment

The diagnostic value of detecting AFP with the indirect immunoradioautography (IR) method has been investigated for teratoblastomas of the testis in adult patients. It is shown that the IR method permits an approximately two-fold increase in the number of serologically diagnosed teratoblastomas, as compared with the standard gelprecipitation method. The results for patients with primary testicular teratoblastomas were 19 AFP-positives in a group of 21 (90.5%). The diagnostic specificity of the test has been lowered insignificantly with the high-sensitivity method: only 8 AFP-positive cases were found in a control group of 215 patients, and all the seropositives suffered from tumors of the gastro-intestinal tract with metastases to the liver. Application of the IR method has greatly increased the possibility of following the course of disease and effectiveness of treatment by the AFP test; in a number of cases it has also permitted a more accurate diagnosis of primary tumor, when metastases are present.     

Concurrent chemoradiotherapy (CRT) with S-1 and cisplatin (CDDP) in patients (pts) with locally advanced head and neck cancer (HNC)

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications. Because the Japanese also have been considered unable to tolerate this regimen, no prospective study of it has been conducted in Japan. Most Japanese patients with locally advanced head and neck cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80 mg/m2). S-1 has shown high activity in HNC with a response rate of 34%. Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported to have good efficacy. With this rationale in mind, we conducted a phase I study of CRT with S-1 and CDDP for unresectable locally advanced squamous cell carcinoma of the head and neck. The CR rate was very promising, though preliminary, and warrants further investigation. The Japan Clinical Oncology Group (JCOG) is planning a multicenter phase II study of concurrent chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.     

Treatment of newly diagnosed multiple myeloma: advances in current therapy

The past decade has seen incredible progress in the treatment of myeloma as a result of more widespread application of autologous stem cell transplantation and introduction of several new drugs. Hence, the survival of patients with this disease has significantly improved during this period. The treatment approach for patients with myeloma has undergone a paradigm shift as a result of the different choices available for treating the patients with newly diagnosed myeloma. In addition, appreciation of the heterogeneity in the outcome of these patients and the impact of genetics on the prognosis has led to efforts at developing a risk-adapted approach to treatment. This article summarizes the recent advances in the treatment of newly diagnosed myeloma and suggests a treatment algorithm for approaching newly diagnosed myeloma.     

The EORTC soft tissue and bone sarcoma group. European Organisation for Research and Treatment of Cancer

The EORTC Soft Tissue Sarcoma Group was founded 25 years ago and has since developed into one of the leading cooperative groups in the research of sarcomas and has members from 40 institutions from 13 countries. The activities of the group have primarily been within the areas of standards for local as well as systemic treatment strategies, new drug development and quality control procedures. The group has a extensive quality control programme involving a strict membership policy, central review of the responses, central review of pathology, use a systemic therapy check-list and on-site monitoring of studies. A large database with over 2500 patients included in EORTC STBSG chemotherapy trials has been developed. So far, the STBSG has conducted more than 40 clinical trials accruing more than 250 patients per year, some of which has been performed in collaboration with other prestigious groups.     

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer

Pemetrexed (Alimta) is a novel multitargeted antifolate that has activity against non-small-cell lung cancer (NSCLC). As a single agent, the response rate is 16%-23%. As second-line therapy, it has a 5% and 14% response rate with pemetrexed in NSCLC patients who have had prior cisplatin or nonplatinum chemotherapy, respectively. Pemetrexed combined with cisplatin has a response rate of 38.9%-44.8%, with a median survival of 8.9-10.9 months. Pemetrexed plus gemcitabine in NSCLC has a response rate of less than 25%. The major toxicity associated with pemetrexed is neutropenia, which may be reduced with vitamin B12 and folate nutritional supplement. Additional studies with pemetrexed in combination with other agents are needed for the treatment of NSCLC patients.     

Treatment of newly diagnosed multiple myeloma: advances in current therapy

The past decade has seen incredible progress in the treatment of myeloma as a result of more widespread application of autologous stem cell transplantation and introduction of several new drugs. Hence, the survival of patients with this disease has significantly improved during this period. The treatment approach for patients with myeloma has undergone a paradigm shift as a result of the different choices available for treating the patients with newly diagnosed myeloma. In addition, appreciation of the heterogeneity in the outcome of these patients and the impact of genetics on the prognosis has led to efforts at developing a risk-adapted approach to treatment. This article summarizes the recent advances in the treatment of newly diagnosed myeloma and suggests a treatment algorithm for approaching newly diagnosed myeloma.

     

Chemoradiation for resectable gastric cancer

The incidence of gastric cancer has been declining in recent years, however, the disease continues to be a worldwide public health problem. About two thirds of patients with gastric cancer undergo surgical resection with curative intent. R0 resection--complete local-regional tumour removal with negative resection margins--is the only curative modality. The optimum extent of lymph-node dissection (D1 vs D2) is controversial. Disease relapse, both local and distant, is common and the 5-year survival rate is disappointing. Adjuvant chemotherapy has been studied extensively in this setting but an effective regimen has not yet been identified. A recent intergroup study has shown that postoperative chemoradiation is effective in improving both disease-free survival (3-year, 48% vs 31%, p<0.001) and overall survival (3-year, 50% vs 41%, p=0.005) compared with surgery alone. Preoperative radiation as a single adjuvant therapy has also yielded improvements in local-regional control, disease-free survival, and overall survival compared with surgery alone. Preoperative chemotherapy or chemoradiation has been accepted to have a theoretical advantage over postoperative therapy and has now been shown to be a feasible option. Its efficacy, however, remains to be tested.     

The Role of Cetuximab in the Management of Non–Small-Cell Lung Cancer

Inhibition of the epidermal growth factor receptor (EGFR) pathway has emerged as a proven strategy for the treatment of advanced-stage Non–Small-cell lung cancer (NSCLC). Cetuximab is a chimeric monoclonal antibody that inhibits EGFR by binding to the extracellular domain of the receptor. The relatively modest anticancer activity as monotherapy in NSCLC has prompted the evaluation of cetuximab as part of novel combination regimens. The safety of cetuximab in combination with the commonly used platinum-based 2-drug regimens in NSCLC has been established in several phase II studies. Recently, the addition of cetuximab to the regimen of cisplatin and vinorelbine resulted in improved overall survival in patients with advanced NSCLC with EGFR-expressing tumors. In contrast, a study in unselected advanced NSCLC patients failed to demonstrate a statistically significant improvement in overall survival with cetuximab in combination with a carboplatin and taxane regimen. It is hoped that identification of predictive biomarkers would lead to the optimal utilization of cetuximab in combination with chemotherapy. The combination of cetuximab with radiotherapy for patients with locally advanced NSCLC has demonstrated promising results in a phase II study and is now being evaluated in a confirmatory trial. This article reviews the clinical data with cetuximab in NSCLC.     

Stem-cell transplantation in chronic lymphocytic leukemia: the time for designing randomized studies has arrived

Stem-cell transplantation in conjunction with myeloablative therapy has evolved as a standard treatment option for patients with several hematologic malignancies, including chemosensitive, relapsed non-Hodgkin's lymphoma and untreated multiple myeloma. The pharmacologic basis for this treatment includes a favorable tumor dose-response curve that abrogates intrinsic drug resistance associated with these diseases and facilitates cure or prolongation of survival even in the absence of a cure. The belief that chronic lymphocytic leukemia (CLL) is a palliative disease of the elderly has been perpetuated, limiting the application of more aggressive therapies. The introduction of fludarabine and its use in combination with other agents has increased the morphologic complete response rate observed in the initial treatment of CLL, providing the rationale to explore further disease-consolidative therapies. Concomitant with this, several phase II studies have demonstrated the feasibility of performing both allogeneic and autologous stem-cell transplantation in patients with CLL. In this regard, allogeneic transplantation has produced prolonged remissions in young patients with relapsed and refractory CLL, but at the cost of high treatment-related morbidity and mortality. Application of "minitransplantation" regimens may temper the frequency of these complications and warrants further study. Autologous stem-cell transplantation has also been explored with promising disease-free survival outcomes in less heavily pretreated patients. However, relapses continue to be the most frequent source of late mortality, as has been observed previously with multiple myeloma. With scientific justification established in similar diseases and demonstrated feasibility with low morbidity, we believe the time for a randomized comparison of standard chemotherapy versus autologous stem-cell transplantation in CLL has arrived. Despite promising results observed with allogeneic transplantation, further refinements that broaden the patient eligibility and lower treatment mortality will be required before similar investigations can occur with this modality.     

Image-guided Adaptive Radiotherapy for Bladder Cancer

Technological advancement has facilitated patient-specific radiotherapy in bladder cancer. This has been made possible by developments in image-guided radiotherapy (IGRT). Particularly transformative has been the integration of volumetric imaging into the workflow. The ability to visualise the bladder target using cone beam computed tomography and magnetic resonance imaging initially assisted with determining the magnitude of inter- and intra-fraction target change. It has led to greater confidence in ascertaining true anatomy at each fraction. The increased certainty of dose delivered to the bladder has permitted the safe reduction of planning target volume margins. IGRT has therefore improved target coverage with a reduction in integral dose to the surrounding tissue. Use of IGRT to feed back into plan and dose delivery optimisation according to the anatomy of the day has enabled adaptive radiotherapy bladder solutions. Here we undertake a review of the stepwise developments underpinning IGRT and adaptive radiotherapy strategies for external beam bladder cancer radiotherapy. We present the evidence in accordance with the framework for systematic clinical evaluation of technical innovations in radiation oncology (R-IDEAL).     

Application of DA/DAPI technique in cancer cytogenetics

The recent advent of banding techniques has facilitated the identification of human chromosomal abnormalities in neoplasias. Utilization of a single technique for the identification of marker chromosomes has caused ambiguity because staining profiles overlap with many other chromosomal regions in the human genome. Thus, the implication of DA/DAPI technique in clinical cytogenetics has been documented by presenting a variety of cases with neoplastic syndromes.     

Confirmation of a prognostic index in primary breast cancer

A prognostic index, previously derived in a group of 387 patients with primary breast cancer, has been recalculated for the same patients with over 5 years further follow-up and shown to be unchanged. The prognostic index has also been applied prospectively to a further group of 320 patients and shown to be similarly effective in identifying patients with either a very good or a very poor prognosis. It has been verified that the index applies to patients with primary breast cancer. Patients have now been divided into 5 prognostic groups, predicting 11% of patients with an almost normal survival and a further 10% with a very poor prognosis. The index is used to stratify patients to study the effects of treatment regimes within groups of similar patients.     

An EORTC gastrointestinal (GI) group randomized evaluation of the toxicity of sequential high dose methotrexate and 5-fluorouracil combined with adriamycin (FAMTX) vs 5-fluorouracil, adriamycin and mitomycin (FAM) in advanced gastric cancer

Until now advanced gastric cancer has been generally treated with the FAM chemotherapy protocol. Due to the relatively low response rates with this protocol we decided to start a randomized prospective phase II trial comparing the FAM with the FAMTX protocol. The primary aim of our trial was to compare the toxicity in both protocols. The FAMTX protocol has been demonstrated to be fully comparable with the toxicity of the FAM protocol. The trial has been extended to a phase III study. With respect to response rates and survival times it is too early for evaluation.     

New treatment strategy of multiple myeloma for cure

Multiple myeloma has long been considered an incurable disease. Indeed, the median survival time in patients treated with conventional chemotherapy has been reported to be about 3 years, and the survival rate decreased consecutively and was about 2 to 3% at 10 years. However, after introduction of autologous stem-cell transplantation in the 1990s, the median survival time was improved to about 5 years. Furthermore, novel drugs have been introduced in the treatment of patients with relapsed/refractory multiple myeloma, and improved the prognosis of these patients. Thalidomide, which has anti-angiogenetic activity, has a 30-40% response rate, and the combination of thalidomide and dexamethasone has a 40-50% response rate. Lenalidomide, which is a thalidomide analog, has a higher efficacy and lower incidence of adverse effects than thalidomide. Bortezomib, which is a proteasome inhibitor and inhibits NF-kappaB activity, has also excellent efficacy like thalidomide. The clinical trials using these drugs for newly diagnosed patients are now ongoing around the world, and show very excellent results. The good combination of stem-cell transplantation and novel drugs may well improve the prognosis of patients with multiple myeloma, and induce a cure,especially in young patients.     

Calcification in a Mucus-Producing Carcinoma of the Stomach: Case Report

Another case of calcification in a gastric carcinoma is recorded, bringing the total in the English literature to 13. In all cases the calcification has been noted in the left hypo-chondrium and has been of a punctate type. The diagnosis has been confirmed by barium meal examination, which has revealed an obvious carcinoma of the stomach, the calcification being in the thickened gastric wall. In each case the gastric tumour has been an adenocarcinoma with a tendency towards marked mucus production.     

Chemotherapy of sarcomas.

The development of intensive treatment techniques with combination chemotherapy, radiation, and selected surgery has produced dramatic improvements in the treatment of soft tissue sarcomas. This has been best demonstrated in the long-term disease-free survival of a majority of children with inoperable or metastatic embryonal rhabdomyosarcoma treated with VAC chemotherapy (vincristine, actinomycin D, and cyclophosphamide). The addition of adriamycin and imidazole carboxamide to the combination therapy program for adults with soft tissue sarcomas has resulted in significant improvements in their response rates as well.     

The role of Zyflamend, an herbal anti-inflammatory, as a potential chemopreventive agent against prostate cancer: a case report

Correlation between dietary intake and occurrence of prostate cancer has gained significant support in recent years. Although a direct correlation has yet to be proven between inflammation and prostate cancer, chronic or recurrent inflammation has been hypothesized to be the major predisposing factor for this disease. The authors have been studying Zyflamend, a novel herbal anti-inflammatory mixture, as a potential chemopreventive agent in a phase 1 trial for patients diagnosed with prostatic intraepithelial neoplasia. They report the results of the first patient who has completed the 18-month study in which 24 patients were assigned to a cohort and placed on successive herbal supplement regimen starting with Zyflamend alone.     

The Use of Intravenous Methotrexate in the Treatment of Ectopic Pregnancy

Abstract

Cryptococcosis is a disseminated fungal disease typically associated with immuno-suppression and characterized by high mortality rates. Cryptococcus neoformans has been reported to be isolated from blood cultures in around 20% of patients with cryptococcosis, and cryptococcemia has been correlated with poor prognosis.

We report a case of fatal C. neoformans fungemia in a neutropenic patient with a history of chronic lymphocytic leukemia treated with alemtuzumab. The patient presented with loss of consciousness and died after 5 days of antifungal therapy with liposomal amphotericin B. The international literature regarding opportunistic infections after immunosuppressive therapy with alemtuzumab with particular attention on fun-gal infections has also been reviewed.     

Routine clinical application of the lymphocyte fluorescence polarization test for malignant disease

The technique of Lymphocyte Fluorescence Polarization (LFP) can confirm or exclude the presence of malignant disease. The results from tests on a total of 566 subjects showed a false-positive rate of 3.8% and a false-negative rate of 2.2%. The LFP test has been used as an aid in the differential diagnosis of patients whose symptoms are not typical of primary or recurrent malignant disease. In over 40 such cases there has been total agreement between the LFP results and subsequent clinical or pathological investigations. The LFP Test has been used to monitor the response of cancer patients to various therapeutic regimes. Ovarian cancer patients giving negative LFP results after treatment with Cisplatin have been found free of disease at laparotomy, indicating that LFP may be an acceptable alternative to the surgical investigation. The LFP test has been shown to provide information of much value in the management of patients with malignant disease.     

Three decades of chemotherapy for childhood cancer: from cure 'at any cost' to cure 'at least cost'

The prognosis for childhood malignancy has improved substantially over the last 30 years. This has been principally due to the use of chemotherapy, centralization of care and treatment by standard protocols. With increasing numbers of children and adolescents cured of cancer there has been an increased awareness of the late effects of therapy. The recent recognition of disease-specific prognostic factors has permitted the subclassification of tumours into good and bad risk. The aim for those malignancies associated with a good outcome is the reduction of late adverse effects, eg intellectual impairment in children with acute lymphoblastic leukemia receiving central nervous system irradiation. In those diseases which have a poor prognosis with present therapy, new innovative and intensive regimens are being investigated in randomized trials. Neuroblastoma is a chemosensitive tumour but there has been little success in translating response into improvements in long-term cure. In poor prognosis neuroblastoma conventional combination chemotherapy, high dose therapy with autologous bone marrow rescue as consolidation and more recently high dose, or high dose rapid schedule, chemotherapy as initial treatment have been sequentially evaluated. In paediatric brain tumours only now are well designed phase II studies being undertaken and problems associated with the classification and evaluation of response to therapy are being addressed. In the past 30 years much of the success with childhood cancer has been largely empirical and the hope for the future is that there will be a more scientific approach to the chemotherapy of childhood malignancy.