Hormone replacement therapy in previously treated breast cancer patients.

We report our experience with 25 women previously treated for breast cancer who subsequently received hormone replacement therapy (HRT) for the relief of menopausal symptoms and the prevention of postmenopausal cardiovascular disease and osteoporosis. Two patients had in situ disease, 13 had stage I disease, 7 had stage II disease, 1 had stage III disease, and 2 had invasive cancer of undetermined stage. Seventeen patients (group I) began HRT less than 24 months after primary breast cancer therapy, and 8 patients (group II) began HRT more than 24 months after breast cancer therapy. The HRT-free interval for group I patients averaged 7.9 months and for group II patients averaged 64.5 months. The average period of observation while receiving HRT for the entire group was 35.2 months (range: 24 to 82 months). Three of 25 patients have had a recurrence, all in group I. One patient developed local recurrence after breast conservation treatment, and her condition was salvaged by further wide excision. Two patients developed recurrence after mastectomy, and one patient ultimately died of systemic disease. The overall survival rate for the entire group was 96%. Overall survival of high-risk group I patients, with a mean follow-up of 30.4 months, was 94%. We recognize that this report of HRT in a small group of patients does not have the power to demonstrate an adverse effect of HRT on breast cancer. However, the lack of an obvious adverse effect of HRT in this group of breast cancer patients and the known beneficial effect of HRT on postmenopausal cardiovascular disease and osteoporosis warrant formal prospective trials of HRT in such patients.

Malignant plasma cell tumors in human immunodeficiency virus-infected patients.

The development of malignant neoplasms in patients with the acquired immune deficiency syndrome (AIDS) or with a positive human immunodeficiency virus (HIV) antibody test is a well known phenomenon. According to the guidelines from the Centers for Disease Control (Atlanta, GA), the presence of intermediate-grade or high-grade B-cell non-Hodgkin's lymphoma in HIV antibody-positive patients is considered a diagnostic criterion for AIDS. The authors describe two cases of malignant plasma cell tumors in two young HIV-infected patients. In light of this and other reports of plasma cell tumors in patients at risk for AIDS or with a positive HIV antibody test, the finding of another manifestation of B-cell neoplasia in these patients may enlarge the spectrum of AIDS-related tumors.

Pharmacokinetics of hexamethylmelamine in intralipid following hepatic regional administration in rabbits.

Hexamethylmelamine (HMM) is a cytotoxic agent demonstrated to have broad antitumor activity. Poor solubility in aqueous media has precluded significant evaluation of parenteral administration of this drug. A formulation of HMM dissolved in Intralipid has demonstrated excellent tolerance following parenteral administration. The goal of this study was to evaluate the pharmacology of HMM in Intralipid following hepatic regional administration. The routes of administration were intraarterial via the hepatic artery with and without arterial occlusion, i.v. via the portal and jugular veins, and i.p. All animals received a total dose of 10 mg HMM/kg of body weight. Hepatic extraction of HMM was most evident via the portal vein (PV) route [AUC(PV)/AUC(i.v.) = 0.5; P less than 0.05]. Lower plasma levels and areas under the curve (AUCs) were observed for the hepatic artery and hepatic artery-stop flow groups when compared to i.v., but the difference was not significant. Administration i.p. yielded low plasma levels but a very long half-life (88 min). Hepatic tissue levels were highest in the group receiving HMM by the hepatic artery-stop flow route. We conclude that the HMM-Intralipid mixture is well tolerated, that HMM is extracted to a significant degree by the liver following PV administration, and that an i.p. installation of HMM-Intralipid results in prolonged plasma drug levels. This preclinical study supports further efforts at evaluation of parenteral administration of the HMM-intralipid mixture.

The pharmacokinetics of cisplatin in experimental regional chemotherapy.

Cisplatin (DDP) is attractive for use in regional chemotherapy because of its tendency for protein binding. A study of regional chemotherapy was conducted in rabbits bearing the VX-2 carcinoma. Modes of therapy examined were intravenous (IV), intra-arterial (IA), IA with stopflow, IA with outflow occlusion, and isolation-perfusion (I-P). Each mode was evaluated by examining the pharmacokinetics of DDP in systemic and regional administration and measuring tissue concentrations of DDP. It was observed that the systemic exposure to DDP was significantly less for IA with outflow occlusion and I-P when compared to IV, IA, or IA with stopflow occlusion (P = 0.003). Tumor concentrations were highest with IA infusion with outflow occlusion (P = 0.002) and IA stopflow occlusion (P = 0.03). Tumor tissue concentrations were always higher than adjacent muscle DDP concentrations. The authors conclude that significant pharmacologic advantage can be demonstrated for certain modes of DDP administration in this rabbit model, and that these promising results should be followed by clinical trials.

The pharmacology of hepatic regional administration of cisplatin in a rabbit model.

The pharmacology of hepatic regional administration of CisplatinR (DDP) was examined in a rabbit model. Routes and modes of administration were: IV, hepatic arterial infusion (HAI), HAI with stopflow, HAI with microembolic material [collagen for embolization (CFE)], and portal vein (PV). DDP was rapidly administered, blood samples were drawn over 45 minutes, and hepatic tissue was obtained. Filterable plasma DDP levels were measured by HPLC. Hepatic DDP levels were determined by atomic absorption spectroscopy. All modes of regional administration yielded significantly higher hepatic DDP levels when compared to tissue levels following IV administration. Only the PV and HACFE routes resulted in significantly less systemic drug exposure (AUC) when compared to IV administration. These data indicate a relative pharmacologic advantage of 1.8 for HAI, 3.4 for PV, 1.8 for HAI stopflow, and 4.3 for HACFE compared to IV DDP administration. This pre-clinical study demonstrates substantial pharmacologic advantage for PV and HACFE routes of DDP administration and suggests that clinical trials based on this information be considered.

Phase II trial of PALA in lymphoma: an Eastern Cooperative Oncology Group study.

A phase II trial of PALA in malignant lymphoma was carried out by the Eastern Cooperative Oncology Group. The occurrence of hematologic toxicity in 17 of 35 patients in the study was noteworthy and was possibly related to prior therapy and/or marrow involvement. The finding of thromboembolic phenomena in four of five autopsied patients was also noteworthy. No antitumor activity was recorded. This experience discourages further trials of PALA in patients with malignant lymphoma.

Intravenous metoclopramide. An effective antiemetic in cancer chemotherapy.

An open-label clinical trial was conducted to test the safety and efficacy of intravenous metoclopramide monohydrochloride in preventing chemotherapy-induced nausea and vomiting. Thirty-eight patients received a total of 83 assessable courses of chemotherapy with cisplatin alone or in combination with other cytotoxic agents. In 19 of 38 patients (50%) or 40 of 83 courses (48%), nausea or vomiting did not occur ("total protection") and in six of 38 patients (16%) or 19 of 83 courses (23%), emesis occurred one of two times ("major protection"). Thus, 25 of 38 patients (66%) receiving 59 of 83 courses (71%) of cisplatin-containing chemotherapy attained either total or major antiemetic protection with metoclopramide. In those patients who received multiple courses of chemotherapy, antiemetic protection afforded by metoclopramide remained unabated. At this dosage, the drug was well tolerated with minimal side effects. Intravenous metoclopramide is consistently effective in preventing emesis associated with cisplatin when used either alone or in combination with other cancer chemotherapy agents that are in themselves emetogenic.

Leptomeningeal myeloma.

Multiple myeloma commonly produces neurologic symptoms when it involves the cranium or vertebrae, but rarely invades the CNS or meninges. Intracranial or intraspinal myeloma without lesions in the adjacent bone is extremely rare. To our knowledge, there are only ten reported cases of isolated myeloma in dura and/or brain, and only two limited to the leptomeninges. We wish to report the third case of isolated leptomeningeal myeloma. Both myeloma cells and abnormal globulins were present in the CSF, but absent from serum and bone marrow. Analysis of these 13 cases in dura, brain, or leptomeninges strongly supports the concept that abnormal proteins do not reach the CSF from the serum but are produced by myeloma cells in situ.