Recent advances in AIDS vaccine research and development.

There is an urgent need for a prophylactic vaccine to protect individuals from AIDS and to help abate the growing epidemic. In October 1993, the Conference on Advances in AIDS Vaccine Development reviewed the state-of-the-art in vaccine research and confirmed both the progress that has been made and the challenges that remain. Approximately 12 candidate vaccines are now in phase I/II clinical trials. To date, these products appear to be safe and capable of eliciting immune responses in vaccinees. Other vaccine strategies in development include the use of new formulations and the design of vaccine products capable of inducing a mucosal immune response. Progress has also been made in the establishment of domestic and international sites at which efficacy trials can be conducted when appropriate vaccine candidates are identified, and preparatory activities at these sites are ongoing. The possibility that one or more candidates may enter efficacy trials within the next 2 years underscores numerous issues that must be considered in preparation for these trials. These include the importance of ease of vaccine administration and cost, and an array of social, legal, and ethical issues of concern to those individuals who will be asked to participate in efficacy trials. The purpose of this article is to highlight recent advances in vaccine research and development and to define the complex factors that will impact the NIAID's position on advancing candidates into phase III trials.

Small cell bronchogenic carcinoma.

We have attempted to highlight the most important aspects of SCBC in this review. The significant strides made in a variety of areas have been associated with increased response rates and survival as well as with a prolonged disease-free interval in a fraction of patients. The consensus is that 50% or more of patients with LD can achieve a CR, with an overall objective response rate of 80% or greater and a median overall survival of 14 months or longer. Furthermore, 15% to 20% of such patients may expect a disease-free interval of at least three years that appears to be associated with cure in at least some of these patients. Patients with ED may experience a 20% or greater CR, an 80% or greater objective response, and have a median overall survival of at least seven months. Extensive research is ongoing in a variety of areas. Further refinements in developing more effective chemotherapeutic regimens are likely, as is obtaining new information concerning the intensity, duration, and selection of chemotherapeutic agents and their role in relationship to radiotherapy. Improvement in radiotherapy techniques may lead to improved therapeutic results. Only recently has a reevaluation of the role of surgery in SCBC begun to take place. Also, several new areas of investigation are on the horizon, ranging from improved staging with thoracic and abdominal computed tomography to the role of warfarin, monoclonal tumor antibodies, and several currently investigational chemotherapeutic and biologic response modifier agents.

Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU).

We evaluated the risk of acute nonlymphocytic leukemia, acute myelodysplastic syndrome, and preleukemia in 3633 patients with gastrointestinal cancer who were treated in nine randomized clinical trials. Among 2067 patients given semustine (methyl-CCNU) as adjuvant therapy, leukemic disorders developed in 14, whereas only one leukemic disorder (acute nonlymphocytic leukemia) occurred among 1566 patients given other therapies (relative risk = 12.4; 95 per cent confidence interval = 1.7 to 250). The six-year cumulative mean risk (+/- S.E.) of acquiring a leukemic disorder after treatment with semustine was 4.0 +/- 2.2 per cent; the incidence rate was 2.3 cases per 1000 persons per year. Risk increased significantly with time after treatment. The risk of leukemic disorders did not differ according to sex, race, age at treatment, or initial tumor type, nor was it enhanced by concomitant radiotherapy or immunotherapy. In addition, no excess of acute nonlymphocytic leukemia was seen in 44,370 patients treated for gastrointestinal cancer in Connecticut during the period 1935 to 1974, before the advent of nitrosourea chemotherapy. This study provides quantitative evidence that nitrosoureas are leukemogenic in human beings and confirms previous observations that adjuvant chemotherapy with alkylating agents may increase the risk of leukemia.

Phase II studies of methyl glyoxal bis-guanylhydrazone (NSC 32946) in carcinoma of the colon and lung.

We have tested methyl glyoxal bis-guanyl hydrazone (NSC 32946) for antitumor activity in patients with colorectal carcinoma and non-small cell bronchogenic carcinoma. The drug dose was 500 mg/m2 administered by single weekly injection, and with a provision dose escalation. No responses were seen in 38 evaluable patients with colorectal cancer, including 17 who had received no prior chemotherapy. Three responses were seen among 42 patients with bronchogenic carcinoma. These included one each with epidermoid carcinoma, adenocarcinoma and large cell anaplastic carcinoma. None of these responders had received prior chemotherapy. Toxicity of the drug was predominantly gastrointestinal, namely nausea, vomiting and diarrhea, and tended to increase with repeated drug doses. Neurologic symptoms of various sorts were also prominent. We conclude that methyl-G is of marginal benefit in this dose and schedule to patients with bronchogenic carcinoma.

Optic neuritis and systemic lymphoma.

A 26-year-old man with stage IV poorly differentiated lymphocytic lymphoma complained of visual loss of two weeks' duration. Examination revealed visual acuity of light perception in the right eye secondary to optic neuritis and other tests revealed the presence of lymphomatous leptomeningeal infiltration. Combined treatment with intrathecal methotrexate, prednisone, and whole brain radiation resulted in rapid long-lasting recovery of visual function of the right eye. The cerebrospinal fluid contained a large amount of thymus-derived lymphocytes and the subsequent clinical course observed with characteristic of T-cell or malignant lymphoblastic lymphoma.