Institute of Cancer Research in the United Kingdom extended the clinical usefulness of the platinum compounds with their development of carboplatin, a cisplatin derivative with broad antitumour activity and comparatively less nephrotoxicity. Nitrosoureas A second group with an NCI contract, led by John Montgomery at the Southern Research Institute, synthesized nitrosoureas, an alkylating agent which cross-links DNA. Fludarabine phosphate, a purine analogue which has become a mainstay in treatment of patients with chronic lymphocytic leukaemia, was another similar development by Montgomery. Anthracyclines and epipodophyllotoxins Other effective molecules also came from industry during the period of 1970 to 1990, including anthracyclines and epipodophyllotoxins — both of which inhibited the action of topoisomerase II, an enzyme crucial for DNA synthesis. Supportive care during chemotherapy As is obvious from their origins, the above cancer chemotherapies are essentially poisons. Patients receiving these agents experienced severe side-effects that limited the doses which could be administered, and hence limited the beneficial effects. Clinical investigators realized that the ability to manage these toxicities was crucial to the success of cancer chemotherapy. Several examples are noteworthy. Many chemotherapeutic agents cause profound suppression of the bone marrow. This is reversible, but takes time to recover. Support with platelet and red-cell transfusions as well as broad-spectrum antibiotics in case of infection during this period is crucial to allow the patient to recover. Several practical factors are also worth mentioning. Most of these agents caused very severe nausea (termed chemotherapy-induced nausea and vomiting (CINV) in the literature) which, while not directly causing patient deaths, was unbearable at higher doses. The development of new drugs to prevent nausea (the prototype of which was ondansetron) was of great practical use, as was the design of indwelling intravenous catheters (e.g. Hickman lines and PICC lines) which allowed safe administration of chemotherapy as well as supportive therapy. Bone marrow transplantation One important contribution during this period was the discovery of a means that allowed the administration of previously lethal doses of chemotherapy. The patient's bone marrow was first harvested, the chemotherapy administered, and the harvested marrow then returned to patient a few days later. This approach, termed autologous bone marrow transplantation, was initially thought to be of benefit to a wide group of patients, including those with advanced breast cancer. However, rigorous studies have failed to confirm this benefit, and autologous transplantation is no longer widely used for solid tumors. The proven curative benefits of