Terence S. Herman

Involvement of the central nervous system by non‐Hodgkin's lymphoma. The southwest oncology group experience

Fifty (5%) of 1039 patients with non‐Hodgkins lymphomas registered on two Southwest Oncology Group clinical trials between 1972 and 1977 developed evidence of central nervous system (CNS) lymphoma. Thirty‐nine patients (3.7%) had leptomeningeal involvement, 10 patients (1%) had focal cerebral involvement and 2 patients (0.1%) had spinal cord compression. Cytologic examination of the cerebrospinal fluid (CSF) was the most reliable diagnostic technique. Patients with diffuse histologies and those with nodular histiocytic lymphoma had the highest incidence of CNS disease. Diffuse histiocytic lymphoma accounted for 22 patients with CNS involvement. Lymphoblastic lymphoma, convoluted type, was found in 6 patients, although in none was the diagnosis established prospectively. Patients who developed CNS lymphoma usually had extranodal disease and systemic symptoms at initial staging (90% stage IV, 54% “B” symptoms). The most commonly involved extranodal sites included the bone marrow (56%), gastrointestinal tract (26%), skin (18%), and lung (14%). CNS lymphoma was observed at all times during the clinical course but was most common in patients with active, poorly controlled disease. In 13 patients (26%), however, CNS lymphoma was the first sign of relapsing lymphoma. Median survival after recognition of CNS lymphoma was 2 months. The incidence of CNS disease was similar for 5 remission induction regimens employed, but maintenance chemotherapy with vincristine, prednisone and parenteral cytosine arabinoside appeared to substantially reduce the incidence of late CNS relapse (1 of 90 patients) compared to maintenance treatment with oral cyclophosphamide in place of cytosine arabinoside (9 of 90 patients, p = 0.02). This study indicates that there is a subgroup of patients with readily identifiable clinical and pathologic features who might benefit from prophylactic therapy to prevent CNS lymphoma.

Superiority of Nabilone over Prochlorperazine as an Antiemetic in Patients Receiving Cancer Chemotherapy

Two double-blind, crossover trials comparing the antiemetic effectiveness of nabilone, a new synthetic cannabinoid, with that of prochlorperazine were conducted in patients with severe nausea and vomiting associated with anticancer chemotherapy. Of 113 patients evaluated, 90 (80 per cent) responded to nabilone therapy, whereas only 36 (32 per cent) responded to prochlorperazine (P less than 0.001). Complete relief of symptoms was infrequent, occurring only in nine patients (8 per cent) given nabilone. When both drugs were compared, both nausea (P less than 0.01) and vomiting episodes (P less than 0.001) were significantly lower in patients given nabilone. Moreover, patients clearly favored nabilone for continued use (P less than 0.001). Predominant side effects noted by patients were similar for both agents and included somnolence, dry mouth and dizziness but were about twice as frequent and more often severe in patients receiving nabilone. In addition, four patients (3 per cent) taking nabilone had side effects (hallucinations in three, hypotension in one) that required medical attention. Euphoria associated with nabilone was infrequent (16 per cent) and mild.

Adriamycin/cis-platinum/cyclophosphamide combination chemotherapy for advanced carcinoma of the parotid gland.

Five patients were treated with a combination of Adriamycin/cis‐platinum/cyclophosphamide for faradvanced and/or recurrent cancers of the salivary gland. Adriamycin, 40 mg/m2, and cis‐platinum, 50 mg/m2, were given on day 1; cyclophosphamide, 200 mg/m2 daily for four days, was given by mouth on the third to sixth day of each monthly therapy course. Two patients achieved a complete remission, each lasting five months, and the three others had partial remissions from one to seven months (median six months) in duration. Therapy was well tolerated. Severe nausea and vomiting occurred on the first day of therapy but was self‐limited. There was only mild to moderate leukopenia, no significant thrombo‐cytopenia or elevations of serum creatinine, and no evidence of dose‐limiting peripheral neuropathy. Adriamycin/cis‐platinum/cyclophosphamide chemotherapy appears to be effective in the treatment of advanced parotid gland cancers.

Polyamines and Polyamine Biosynthesis in Cells Exposed to Hyperthermia

The issue of how polyamines act to sensitize cultured cells to the lethal effects of hyperthermia was investigated using Chinese hamster cells which were induced to express thermotolerance. Intracellular levels of these naturally occurring polycations were manipulated in certain situations by treating whole cells with methylglyoxal bis-(guanylhydrazone), an inhibitor of the S-adenosyl-L-methionine decarboxylases. Exogenous spermine as low as 100 microM in the culture media dramatically sensitized cells expressing thermotolerance to the lethal effects of subsequent 42 degrees C exposures. When thermotolerance was differentially induced in cultures exposed to 42.4 degrees C by varying the rate of heating from 37 to 42.4 degrees C, the most resistant cells had the highest levels of intracellular spermidine and spermine. This finding was explainable in part by the observation that the putrescine-dependent S-adenosyl-L-methionine decarboxylase activity was minimally affected in cells expressing the greatest degree of thermotolerance. When this enzyme activity was inhibited by drug, lowered intracellular polyamine levels did not correspond with subsequent survival responses to heat. Interestingly, cultures treated with methylglyoxal bis-(guanylhydrazone) 24 hr previous to heat exposure showed a reduced capacity to express rate of heating-induced thermotolerance. Together, these results demonstrate that the polyamines, especially spermidine and spermine, enhance hyperthermia-induced cell killing by some mechanism involving the plasma membrane. Further, our data suggest that methylglyoxal bis-(guanylhydrazone) can act to affect thermal responses by a mechanism(s) other than modification of intracellular polyamine levels.

Systematic restaging in patients with Hodgkin's disease. A Southwest Oncology Group study

Eighty‐two patients with advanced Hodgkins disease who were in apparent complete remission (CR) after receiving 10 courses of combination chemotherapy were systematically reevaluated for persisting disease. Occult Hodgkins disease was found in 10 (12%) of these patients and was predominantly present in nodal sites (91%) which were known to have been involved at initial staging (100%). Repeat chest radiography, Gallium‐67 tumor scanning and lymphography were the most helpful procedures for detecting residual disease. Nine of the 72 (13%) patients felt to be free of disease after negative restaging subsequently relapsed within 8 months. Sites of early relapse, like the sites of disease found at restaging, occurred almost always in previously involved nodal areas. We conclude that systematic restaging should be incorporated into subsequent lymphoma trials in order to define more clearly complete remission and that every patient treated for lymphoma should undergo a careful restaging evaluation before therapy is discontinued. Cancer 42:1976‐1982, 1978.