Phase II trial of topotecan in advanced or metastatic adenocarcinoma of the pancreas.

PURPOSE: A phase II trial of topotecan, an inhibitor of topoisomerase I, was conducted in patients with advanced or metastatic adenocarcinoma of the pancreas to determine the activity and toxicity of topotecan. PATIENTS AND MATERIALS: 35 patients, previously untreated with chemotherapy, received topotecan 1.5 mg/m2/d for five days intravenously and repeated every 21 days. Patients were assessed for response after 3 cycles. Those with either clinical response or stable disease received additional cycles of the drug until toxicity developed or disease progression occurred. RESULTS: Among 30 patients evaluable for response there were no complete responses and 3 partial responses (10%) for a total response rate of 10% (95% confidence interval = 0-20.6%). Stable disease for at least eight weeks was seen in 11 patients (36%). Median survival was 19 weeks (95% confidence interval 11 to 26 weeks). Therapy was generally well tolerated, with reversible granulocytopenia being the most common toxicity. CONCLUSION: Topotecan given on a 5 day, short infusion schedule, demonstrated limited activity in pancreatic carcinoma with minimal toxicity. Further exploration of topotecan in pancreatic carcinoma using different dosing schedules is warranted.

Inhibitor treatment using unactivated prothrombin complex concentrates: the Pennsylvania experience--1978-1982.

Data were analyzed on 48 patients with Factor VIII:C inhibitors, 31 of whom were treated with more than 6.7 million units of unactivated prothrombin complex concentrates (PCC) during the years 1978 through 1982 for more than 1,000 bleeding episodes. Twelve of the patients who were on home therapy used 3.1 million units, or 47% of the total PCC usage. Only one patient had a severe life-threatening allergic reaction to PCC, and no thrombotic complications were observed, supporting the concept that these products are safe when used in doses of 50-75 u/Kg. Fifty percent of hemarthroses and 65% of muscle hemorrhages were treated with no more than two infusions per episode, suggesting that PCC was effective at least half of the time. Comparison of the number of days hospitalized per year for inhibitor and non-inhibitor patients also indicated that PCC was effective, although not as effective as AHF therapy in non-inhibitor patients. The life styles of PCC treated patients were comparable to what might be expected for non-inhibitor patients with severe disease, and no deaths were attributed to PCC treatment failure during the four year period. Of major concern, however, was the cost of therapy. In 1981-82, the average use of PCC for inhibitor patients was 106,000 units per treated patient per year, compared to 40,000 AHF units for all Factor VIII deficient treated patients per year. Much of this usage was for recurrent hemarthroses in a small number of patients requiring eight or more infusions per episode.

Liver dysfunction in Pennsylvania's multitransfused hemophiliacs.

Transaminase values [alanine amino transferase (ALT) and aspartate amino transferase (AST)] and markers for hepatitis B were serially determined in 558 hemophiliacs exposed to blood products. Hepatitis B surface antigen (HBsAg) persistent for over 12 months was present in 6% of the patients. Antibody to hepatitis B surface antigen (anti-HBs) was noted in 90% of the 259 patients treated with factor VIII or IX concentrates but in only 49% of the 43 patients treated with fresh frozen plasma (FFP) or cryoprecipitate. Persistently abnormal transaminase values were noted in 31% of the patients treated with commercial concentrates but in only one (2%) of the patients exposed to cryoprecipitate or FFP. This difference continued even when the two groups of patients were matched for the amount of blood products, up to 50,000 units, which they had received in the study period. In the concentrate-treated patients, no correlation could be found between transaminase values and the number of units of factor VIII or IX they had received during the six years of the study (1973-1978).

Hepatitis B virus, hepatitis A virus and persistently elevated aminotransferases in hemophiliacs.

To determine the exposure to hepatitis A and hepatitis B viruses (HAV, HBV) following intravenous replacement therapy in patients with classic hemophilia and to assess the role of these viruses in persistently elevated aminotransferases, sera were studied from 136 patients from 9 months to 67 years of age were transfused with either single-donor cryoprecipitate (CRYO) or Antihemophilic Factor Concentrate (AHF) for periods ranging from a few months to 15 years. Serologic evidence of past or present infection with HBV was detected in 90% of all 136 patients and in 85% of those 34 patients 10 years of age or younger. Sixty-four percent of those with serologic markers of hepatitis B had high titers of antibody to the hepatitis B surface antigen and low titers of antibody to the hepatitis B core antigen. These findings are consistent with the known high frequency of early exposure to HBV in hemophiliacs receiving replacement therapy and with recovery from these hepatitis B infections. Sixteen percent of these patients had persistently elevated aminotransferase levels; HBV could not be implicated as the cause of the enzyme elevations in most of these cases.

The Pennsylvania hemophilia program 1973-1978.

In Pennsylvania, the prevalence of hemophilia is one per 10,000 males. Factor VIII deficiency is five times more frequent than Factor IX deficiency, and 34% of the patients have no relatives affected with the disease. The mean age is 23 years old, and 50% of the patients are less than 20 years old. Approximately one-third of the patients with Factor VIII deficiency and one fourth of the patients with Factor IX deficiency have levels of less than 0.01 mu/ml. By clinical criteria, 55% of those with Factor VIII deficiency are severe compared to 45% of those with Factor IX deficiency. Factor VIII-deficient patients are treated an average of 18 times per year compared to ten times per year for patients with Factor IX deficiency. Hemarthroses account for 70% of the hemorrhages treated and for 40% of the concentrate usage. Home therapy patients use an average of 45,950 Factor VIII units per year at a cost of ø170 per patient and their use accounts for 60% of the total Factor VIII usage of 1.7 million units. Less than five days per patient per year are lost from school or work because of bleeding, and patients are hospitalized for bleeding an average of only two to three days per patient year. Adverse immediate reactions to therapy are infrequent. Five percent of patients have persistence of the hepatitis B virus, and 7.5% have inhibitors. The mortality rate is 0.04% per year, with half of the deaths being hemophilia-related.

Leukemic reticuloendotheliosis: report of a case with peripheral blood remission on androgen therapy.

Leukemic reticuloendotheliosis (LRE) has been generally considered to be poorly responsive to therapy other than splenectomy. The patient presented below developed a complete peripheral blood remission after prolonged therapy with an androgen (oxymetholone). There is very little published experience with androgen therapy in LRE. The experience with this patient suggests that androgens may produce a clinical remission by inducing significant improvement in the peripheral blood in some patients with this disease.

Delayed recurrence and chemotherapy of a granulosa cell tumor.

A case of proved delayed recurrence of a granulosa cell tumor 18 years after initial diagnosis is presented. L-Phenylalanine mustard was given after radiation was refused for the unresectable mass. A prolonged complete remission was produced. The present status of palliative therapy of recurrent granulosa cell tumor is discussed with a request for the reporting of experiences with more patients treated with chemotherapy.

The phase II evaluation of Bacillus Calmette-Guerin plus megestrol acetate in patients with metastatic renal adenocarcinoma.

The case is reported of a patient with pulmonary metastases from a renal adenocarcinoma who experienced subjective improvement and objective tumor regression on Bacillus Calmette-Guerin (BCG) and megestrol acetate therapy. In a subsequent Phase II trial, no objective responses were noted among 15 patients treated with megestrol acetate (160 mg/day X 56 days) and BCG (five immunizing doses intradermally, every 2 weeks X 5). It is concluded that this treatment regimen is not clinically useful in patients with metastatic renal adenocarcinoma.