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Previously reported work has indicated that pyridinium bromide perbromide (pyridine hydrobromide perbromide) can be considered a general brominating agent which may be used in brominations ordinarily performed with molecular bromine, such as substitution on aromatic rings and additions to double bonds (1). It is not a specific brominating reagent such as N-bromosuccinimide (2) which is recommended for brominating the allyl position of an olefin. However, the use of peroxide type catalysts (3,4) and aluminum or zinc chloride (5) have extended the scope of the brominations possible with N-bromosuccinimide. An excellent review of the reactions performed with brominating agents other than pyridinium bromide perbromide has been recently written by Carl Djerassi (6).Pyridinium bromide perbromide (7, 8) CsHeNBr • Brz is a red crystalline stable salt having the melting point 135-136°( dec.) with previous softening. The reagent has many advantages over dangerous liquid bromine. It is easily handled and stored and may be conveniently weighed. From its structural formula one would suspect that this perbromide can release free bromine, thus when substituted for bromine in any standard bromination the reaction should be expected to proceed in a normal manner. The experiments reported in this paper seem to verify the efficacy of pyridinium bromide perbromide as a substitute for bromine. The quantities of this reagent used were based on the presence of 45% available bromine, although the supplier has indicated 45-50% bromine available. EXPERIMENTAL Materials: The pyridinium bromide perbromide (PBPB) used in this study was supplied by Jasons Drug Company of Brooklyn, New York.6-Bromo-2-naphthol (9). /S-Naphthol (36 g., 0.25 mole) and 100 ml. of glacial acetic acid were placed in a 500-ml. round-bottom three-neck flask with a condenser, stirrer, and dropping-funnel. Pyridinium bromide perbromide (178 g.) was dissolved in 100 ml. of hot glacial acetic acid, and this solution -was added to the /3-naphthol through the droppingfunnel over a period of twenty minutes. The reaction was cooled slightly so as to effect a gentle reflux. The 0-naphthoI dissolved entirely as the addition took place. Then 25 ml. of water was added to the flask and the entire mixture heated to boiling. After Organic Syntheses (9), 39 g. of mossy tin was added and the mixture was refluxed for two hours. At the end of this period the mixture was cooled to 50°and filtered with suction.To the filtrate was added 1.5 liters of water. A copious white precipitate formed which was washed three times with divided portions of 250 ml. of water. Upon air-drying the solid, 25 g. of a slightly pinkish powder, m.p. 122-124°, was obtained; yield 45.5%. For the classical

Surgical‐adjuvant chemotherapy studies were done with BDF1 mice bearing Lewis Lung (LL) carcinoma implanted intramuscularly (IM). Ten days (D10) after implantation, the tumor‐bearing leg was surgically amputated, and intraperitoneal (IP) drug treatment was started either 3 or 5 days after surgery using single‐dose therapy or intermittent treatment given every 4 days for three doses or daily treatment for five doses. The percentage increase in life span (%ILS) was used as the primary measure for evaluation. Data for 17 clinically active drugs showed that surgical‐adjuvant, single‐agent chemotherapy was markedly effective (%ILS>100) in prolonging the life span of tumor‐bearing animals given BCNU, MeCCNU, and cytoxan; moderate activity (%ILS, 40–100) was obtained with bleomycin and vincristine, and marginal activity (%ILS, 35–40) was observed with 5‐fluorouracil (5‐FU), hexamethylmelamine (HMM), procarbazine, and dibromodulcitol. Surgical‐adjuvant, two‐drug‐combination chemotherapy treatment with bleomycin plus MeCCNU or cis‐platinum [cis‐PT(II)] plus CCNU were more effective than single‐drug chemotherapy in prolonging the life span of tumor‐bearing animals. When used in a surgical‐adjuvant chemotherapy‐treatment schedule, the solid tumor model was found to be sensitive to certain antineoplastic drugs that are of clinical benefit in the treatment of human lung cancer. Thus, the model is potentially useful in the search for newer single agents and combinations of drugs against cancers.

Four antitumor drug combinations which are currently in clinical use were evaluated experimentally using the murine B 16 melanoma model. Bleomycin plus vinblastine produced an increase in life span over either of the two agents alone against both intraperitoneal and subcutaneous B16. This combination also resulted in a large number of long-term survivors. Bleomycin plus cis-platinum produced slight enhancement against subcutaneous B 16, but showed no advantage against intraperitoneal B16. The combination of 5-fluorouracil plus methyl-CCNU significantly increased survival time against the intraperitoneal tumor, and produced long-term survivors as well. The combination of 5-fluorouracil plus BCNU was not more effective than BCNU or 5-fluorouracil alone. These data were compared with the degree of success reported from the clinics against a variety of solid human neoplasms.Cancer 42: 171 1 -1719, 1978.OUR COMBINATIONS CHOSEN FOR analysis F in this report are of particular interest since they are currently being used clinically in the treatment of human solid tumors. The rationale for the conduct of clinical trials with these combinations has been that the regression rates for these drugs alone have been substantial, while their side effects were of different types and occurred at different times. The expectation was that the combinations of agents might produce increased therapeutic benefits without compounding toxicity.One combination tested was bleomycin (NSC 125066) and vinblastine (NSC 49842). Bleomycin is active as a single agent against testicular cancers,21,22 and is a good candidate for combination chemotherapy due to its lack of myel~suppression