In this study, the records of 17 adult patients with medulloblastoma treated with craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed for progression-free survival, overall survival, and toxicity, and the patients were compared with each other and with similarly treated children and adults. Records of patients treated at 3 institutions were reviewed. Seventeen medulloblastoma patients (11 female, 6 male) with a median age of 23 years (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT) plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten patients presented with hydrocephalus, and 7 of them were shunted. Eight patients had gross total resection, 7 had subtotal resection (>50% removed), and 2 had partial resection (<50% removed). Postoperatively, 3 patients had positive cytology and 3 had positive spinal MRI. Five patients were classi ed as good risk and 12 were classi ed as poor risk (Chang staging system). Ten patients were treated with the "Packer protocol," consisting of CSRT plus weekly vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven patients were treated with the Pediatric Oncology Group (POG) protocol, consisting of alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed, with all 8 relapsing at the primary site. Other relapse sites included the leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free survival (Kaplan-Meier) for all patients was 48 months (95% con dence interval, >26 months to ¥). Median relapse-free survival for patients on the Packer protocol was 26 months, and for those on the POG regimen was 48 months (P = 0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were relapse-free on the POG regimen. Two patients relapsed during chemotherapy and 6 relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The estimated median survival of all patients was 56 months (95% con dence interval, 27 to ¥) with 11 patients alive; for the Packer protocol, median survival was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard ratio was 0 (95% con dence interval, 0 to ¥). Toxicity during the Packer protocol was moderately severe, with only 1 of 10 patients able to complete all therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5 had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB) occurred in 7, neutropenia (<500 µl) in 6, thrombocytopenia (<50,000 µl) in 6, nephrotoxicity (>25% ¯by creatinine clearance) in 2, and decreased pulmonary function (diffusing capacity for carbon monoxide ¯>40%) in 1. On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had peripheral neuropathy, and 3 had hearing de cit (>20 dB) or tinnitus. The POG and Packer protocols did not have a statistically signi cant differenc...

The preparation of a number of penicillins with 2-biphenylyl side chains is described. Some of the substituted 2-biphenylcarboxylic acids used as intermediates were synthesized for the first time or were prepared by new methods. These penicillins were active against penicillin G-resistant as well as penicillin G-susceptible staphylococci.The penicillin nucleus, 6-aminopenicillanic acid, which became available in quantity as a biosynthetic product in 1959,1 has been used as the starting material for the chemical preparation of a great number of "semisynthetic" penicillins.2 Previously, total biosynthesis had been the only commercially feasible method for making penicillins, and, out of the limited number so obtainable, only two, penicillins G and V (benzylpenicillin and phenoxymethylpenicillin, respectively), had found wide clinical use. These two antibiotics are active against many Gram-positive organisms, including "susceptible" staphylococci, but they are not effective against the increasing number of "resistant" strains of staphylococci which are being encountered clinically. In this paper the term "susceptible" is used for those staphylococci which are sensitive to penicillins G and V, and "resistant" for those which are unaffected by high levels (e.g. 500-1000 /ml.) of these antibiotics because they have the ability to produce a lactam-opening penicillinase.3The object of the work described in this and the following papers was to find a penicillin with good activity against both susceptible and resistant staphylococci as defined above. An early semisynthetic product, methicillin4 (2,6-dimethoxyphenylpenicillin), has approximately equal activity against these two classes of organism because it is stable to staphylococcal penicillinase.5 However, this activity is low, pre-(1) F.