Joyce L. Eddy

Recombinant Leukocyte A Interferon: An Active Agent in Advanced Cutaneous T-Cell Lymphomas

High-dose recombinant leukocyte A interferon (50 X 10(6) U/m2 body surface area, intramuscularly, three times weekly) was tested in a clinical trial involving patients with advanced cutaneous T-cell lymphomas to determine its effectiveness and toxicity. All 20 patients had advanced stages of disease refractory to two or more standard therapies. Objective partial remissions lasting 3 months to more than 25 months (median, 5 months) were documented in 9 patients. The major dose-limiting toxicity was a severe influenza-like syndrome with malaise, anorexia, depression, weight loss, and decreased performance status; this effect was reversible after dose reductions in all patients and did not recur with re-escalation of doses in 10 patients. This interferon preparation is highly effective in the treatment of advanced refractory cutaneous T-cell lymphomas, and new schedules to reduce toxicity and achieve complete responses, combined treatment with chemotherapy or serotherapy, and its use in earlier stages of disease should be investigated.

Histopathologic staging at initial diagnosis of mycosis fungoides and the Sézary syndrome. Definition of three distinctive prognostic groups.

STUDY OBJECTIVE To determine the optimal staging evaluation at the time of initial diagnosis of mycosis fungoides or the Sézary syndrome. DESIGN Retrospective review of a uniformly staged inception cohort. SETTING Single-institution tertiary care center. PATIENTS 152 consecutive patients who had mycosis fungoides with or without the Sézary syndrome within 6 months of the initial definitive diagnosis. INTERVENTION A detailed staging evaluation including physical examination, routine laboratory studies, chest roentgenogram, lymphangiogram, peripheral blood smear, lymph node biopsy, bone marrow aspirate or biopsy, and liver biopsy in selected patients. MEASUREMENTS AND MAIN RESULTS Univariate adverse prognostic features at initial diagnosis in patients with mycosis fungoides included (P less than 0.01) one or more cutaneous tumors or generalized erythroderma, adenopathy, blood smear involvement with Sézary cells, lymph node effacement, eosinophilia, and visceral involvement. Important, independent prognostic factors in a multivariate analysis are the presence of visceral disease and type of skin involvement. CONCLUSIONS A staging system based on histopathologic evaluation of skin, lymph nodes, blood, and visceral sites provides more comprehensive prognostic information than clinical evaluation of skin disease and adenopathy. Patients may be divided at initial presentation into three prognostic groups: good-risk patients, who have plaque-only skin disease without lymph node, blood, or visceral involvement (median survival, greater than 12 years); intermediate-risk patients, who have cutaneous tumors, erythroderma, or plaque disease with node or blood involvement but no visceral disease or node effacement (median survival, 5 years); and poor-risk patients, who have visceral involvement or node effacement (median survival, 2.5 years).

Septicemic complications of the cutaneous T-cell lymphomas.

The records of 60 consecutive patients with cutaneous T-cell lymphomas were reviewed to determine the incidence, etiology, predisposing factors, therapy, complications and outcome of septicemia. Fourteen (23 percent) patients had 26 septicemias: due to gram-positive cocci in 21 and to gram-negative bacilli in five. The presence of stage IV lymphomatous disease (p 0.032), generalized erythroderma (p less than 0.001), palpable lymph nodes (p 0.014), and histologic involvement of lymph nodes (p 0.023) and peripheral blood (p less than 0.001) identified a subset of patients at high risk for sepsis. Sepsis was correlated with locally infected sites in 77 percent of the episodes. Single antimicrobial therapy was successful in all septicemias due to gram-positive cocci but was accompanied by five secondary gram-negative bacillary superinfections (80 percent fatal). The subsequent mortality in all patients who survived infection (50 percent) indicated their poor over-all prognosis.

Effective treatment of hormonally-unresponsive metastatic carcinoma of the prostate with adriamycin and cyclophosphamide: methods of documenting tumor response and progression.

Combination chemotherapy with Adriamycin and cyclophosphamide was administered to 22 men with progressive tumor following hormonal treatment for metastatic carcinoma of the prostate. Objective partial response was documented in 7 patients (32%); an additional four (18%) had stable disease for a minimum of four months, and 11 (50%) were non‐responders. Patients with partial response had a median survival of 14 months and lived significantly longer than those with no response (median five months); survival of men with stable disease approximated that of partial responders. Serial utilization of mutiple staging procedures during chemotherapy demonstrated that although no single test allowed identification of all patients with objective tumor response or progression, improvement in a median of five parameters could be documented in responding patients. In patients adequately studied at the time of disease progression, deterioration in a median of six tests was found. Serum acid phosphatase, radionuclide bone scan, and plasma carcinoembryonic antigen were the most sensitive procedures which detected both objective tumor response and progression. Toxicity of chemotherapy was acceptable except in patients with prior radiation therapy. Administration of Adriamycin and cyclophosphamide was associated with clinical benefit in half of our patients with hormone‐resistant prostatic cancer. Tumor response and progression can best be objectively assessed if several staging procedures are serially employed during treatment.

Response to Thoracic Radiotherapy in Patients with Small Cell Carcinoma of the Lung After Failure of Combination Chemotherapy

Chest radiotherapy was given to 23 patients with small cell carcinoma of the lung after development of progressive intrathoracic tumor on chemotherapeutic regimens. Treatment schedules were variable, with a median dose of 3,200 rad (32 Gy) in 10 fractions. Objective tumor regression within the radiation portal was observed in 12 patients (52%). Only 3/12 responders did not develop clinically detectable local tumor recurrence before death. Actuarial median time to local tumor progression was 2.5 months in responding and 3.5 months in nonresponding patients. Relapse of intrathoracic small cell carcinoma despite combination chemotherapy was not effectively treated by chest irradiation in the doses utilized. If sustained local palliation is required in this population, higher doses of radiation should be considered.

Combination chemotherapy of hepatocellular carcinoma with doxorubicin and streptozotocin.

Twenty-three patients with unresectable hepatocellular carcinoma were given doxorubicin 60 mg/m2 I.V. day 1 and streptozotocin 0.5 g/m2 I.V. days 1-5 every 3 weeks. This regimen was chosen because of the activity of doxorubicin and nitrosoureas in hepatocellular carcinoma and the ability to administer both drugs in full doses. Twelve patients were fully ambulatory, 14 had normal serum bilirubin, 11 had pathologic proof of cirrhosis, and 11 had no known extrahepatic tumor dissemination. Partial responses lasting 10 and 14 months occurred in two patients (9%), one had stable disease for 15 months, 12 had documented tumor progression within 4 months, and eight died within 6 weeks of the start of chemotherapy. Median survival of all patients was only 3 months (range 0.3-27), but eight (35%) lived more than 1 year. Of these eight, two responded to doxorubicin and streptozotocin, another two to subsequent chemotherapy, and four had no tumor response whatever. More than 90% of the intended doses of doxorubicin and streptozotocin was administered, with severe leukopenia in three patients, moderate thrombocytopenia in one, and moderate proteinuria in nine. There were no drug-related deaths. Various physical, radiologic, and biochemical parameters were employed in detecting tumor response and progression. Initially abnormal physical examination of the liver, hepatic radionuclide and computed tomographic (CT) scans, and serum alpha-fetoprotein levels improved in both responding patients. Tumor progression was detected by physical examination (7/12), radionuclide (10/12) and CT liver scan (3/7), rising alpha-fetoprotein (5/12), and rising carcinoembryonic antigen (3/8). Physical examination and radionuclide liver scan together documented all tumor response and progression. The combination of doxorubicin and streptozotocin has only modest activity in hepatocellular carcinoma and appears no more active than doxorubicin alone.

Evaluation of weekly escalating doses of dichloromethotrexate in patients with hepatocellular carcinoma and other solid tumors

SummaryTwenty-one patients with solid tumors were treated with weekly 6-h intravenous infusions of dichloromethotrexate (DCM), with escalating doses every other week. Frequently observed toxicities included leukopenia, thrombocytopenia, and mucositis. Nausea, vomiting, diarrhea, and elevation of hepatic enzymes and bilirubin occurred less often. The toxicity of DCM was dose-dependent; the maximum tolerated dosage excalation plan was 400 mg/m2x2 weeks, 800 mg/m2x2 weeks, and then 1,200 mg/m2 weekly. Plasma concentrations of DCM were measured during 61 infusions and apparent half-lives determined. The plasma elimination of DCM appears to be similar to that of methotrexate. Three objective tumor responses seen in the seven hepatocellular carcinoma patients treated warrant further investigation.

High-dose methotrexate with leucovorin rescue in patients with unresectable non-small cell carcinoma of the lung.

Thirty‐one patients with unresectable non‐small cell carcinoma of the lung (19 adenocarcinoma, 7 large cell carcinoma, 4 squamous cell carcinoma, 1 mixed histology) were treated with one of two intravenous infusion schedules of high dose methotrexate with leucovorin rescue. First, 14 patients received methotrexate in escalating doses from 1.5 to 12 g/m2 over 6 hours followed immediately with leucovorin 15 mg/m2 for 12 doses every 6 hours; there were no complete or partial responses among these 14 patients. Then, 17 patients were treated with a loading bolus of 50 mg/m2 intravenous methotrexate followed by a 30‐hour continuous infusion of 1.5 g/m2. Leucovorin 15 mg/m2 every 6 hours for 12 doses was begun at the end of the infusion. There were 3 partial responses among the 17 patients in this group. The results demonstrate that both 6‐ and 30‐hour infusions of high‐dose methotrexate regimens can be given safely to middle aged adult patients, but the overall 10% response rate does not appear to be significantly different than the results with standard‐dose methotrexate.

ICRF-159 in advanced gastric cancer. Absence of activity.

ICRF-159, an EDTA derivative antitumor agent, was given to 21 patients with advanced gastric cancer in a weekly dose of 3000 mg/m2. Of the 21 patients, 11 had failed prior drug therapies and 10 were previously untreated. No patient achieved an objective partial response (actual response less than 15% with 95% confidence level). One previously treated patient had a minor response lasting 12 weeks and four patients (three previously untreated) had stable disease lasting 4–8 weeks. Toxicity was acceptable, consisting of mild nausea and moderate myelosuppression. Median survival after treatment was 17.5 weeks in previously untreated patients and 9 weeks in previously treated patients. We conclude that ICRF-159 is inactive in advanced gastric cancer when given on a weekly schedule.