Infusion Of Adriamycin Research Articles

Adjuvant chemotherapy for invasive bladder cancer.

From June 1982 through December 1985, 25 patients who had undergone radical cystectomy with pelvic node dissection for pathologic stage-pT3 or -pT4 and/or N+ disease received adjuvant chemotherapy involving the injection of cis-platinum alone or in combination with adriamycin and 5-fluorouracil (CAF). Thirteen patients also received preoperative adjuvant chemotherapy involving the infusion of cis-platinum, adriamycin, and mitomycin C into the bilateral internal iliac arteries. Postoperative adjuvant chemotherapy was performed using the following two protocols. Protocol 1 (18 cases) consisted of cis-platinum alone being administered every week for 3 weeks and then every month for 1 year. In protocol 2 (7 cases), cisplatinum, adriamycin, and 5-fluorouracil were administered at 3-week intervals on three occasions and then every month for 1 year. Eighteen patients were still alive with no evidence of disease after an average of 26 months. One patient died as a result of factors unrelated to cancer. Local recurrence and distant metastasis occurred in 6 patients, of whom 3 were still alive for an average of 20.7 months. Three patients died of cancer progression after 9, 19, and 21 months. The survival rate for all 25 patients at 50 months was 77%. Nausea and vomiting occurred in most patients during the administration of cis-platinum. Mild myelosuppression developed in a few patients subjected to protocol 2. Our results indicate that adjuvant chemotherapy consisting of the administration of cis-platinum alone or in combination with other chemotherapeutic agents appears to be effective in patients with invasive bladder cancer.

VAD chemotherapy—toxicity and efficacy—in patients with multiple myeloma and other lymphoid malignancies

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.

Numerical simulations of the infusion of adriamycin using a physiological flow model

The antineoplastic drug Adriamycin is administered by short term i.v. infusion. The drug is noted for its acute and chronic cardiotoxicity in addition to its toxicity on the bone marrow and gut. A physiological flow model and computer program, which contains a subprogram for continuous infusion of a drug, was used to simulate the distribution of Adriamycin during infusion in heart, bone marrow, gut, kidney, muscle, skin, liver adn bile. Simulations were carried out for 1, 2, 5, 10 and 20 min of infusion. Computations were made for the concentration of drug in these organs as a function of time over a total period of 48 min. Simulations showed the heart and kidney would contain high concentrations of drug during infusion which rapidly declined upon cessation of infusion. Bone marrow and gut showed a less rapid accumulation and decline. Muscle and skin showed even a slower accumulation and decline. Simulations also showed the effect of altering the rate of infusion on the concentration in the liver and excretion in the bile.

上顎癌の遠隔治療成績

Seventy-three patients with previously untreated carcinoma of the maxillary sinus, treated during an 11-year period were investigated retrospectivelyThe overall three-year and five year survival rates were 51.5% and 42.7% respectively. The five-year survival rate for the group treated with combined therapy consisting of local chemotherapy, radiation and necrotomy was 12.9%, it was 54.8% in the group treated with combined therapy followed by surgery, such as partial or total resection of the maxilla.The most successful treatment was intraarterial infusion of adriamycin (bolus) and 5-FU (continuous), combined with radiotherapy and necrotomy, followed by surgery. The five-year survival rate in this group was 61.7%.

The efficacy and toxicity of VAD in the treatment of myeloma and related disorders.

Impressive results have recently been reported in 29 cases of advanced refractory myeloma treated with 4-d infusions of Vincristine and Adriamycin (VAD). We report our own experience with this protocol in 13 cases of myeloma and related lymphoproliferative disorders. In 2 of these cases, VAD was used as first line treatment. Objective responses were seen in two-thirds of cases and the major complication of therapy was infection, predominantly bacterial in nature.

Management of osteogenic sarcoma patients.

The experience in the management of 246 patients with local osteogenic sarcoma and 67 patients with pulmonary metastases in the All-Union Oncologic Research Center, AMS USSR, is presented here. All the patients underwent surgery, but starting in 1974, various modalities of adjuvant chemotherapy (not randomized) were applied in addition. In the surgery alone group, prognosis was very poor: only 7.0% of patients survived free of disease 5 years from the primary tumor treatment. Adjuvant chemotherapy (adriamycin + vincristine + melphalan + cyclophosphamide) following amputations increased this rate to 34.0%; combining segmental resections of an affected bone with preoperative intraarterial adriamycin infusion and radiation (36 Gy) increased the rate to 35.5%. In patients with grade 4 tumor damage (tumor cells are not found upon examination of a large number of sections), the rate increased to 57.9% (P less than .05). Another regimen of adjuvant chemotherapy (platidiam or cisplatin + adriamycin + cyclophosphamide) gives a chance to 78.8% of patients to survive 1 year free of metastases. The same chemotherapy regimen enables us to achieve an objective effect in 30.8% of patients with pulmonary metastases, and its combination with surgical metastasis ablation makes it possible to obtain a complete remission, lasting from 2 to 46 months (average 13.9 months). Toxic manifestations of the chemotherapy regimens considered are moderate. Prognosis in adjuvant chemotherapy is related to age, tumor site, its local dissemination, and morphologic type of osteogenic sarcoma.

Limb salvage in extremity soft-tissue sarcoma: combined modality therapy.

Thirty-two consecutive patients with high-grade soft-tissue sarcoma of an extremity were treated preoperatively with concomitant intra-arterial infusion of Adriamycin (doxorubicin) (10 mg/m2 daily for 10 days) and radiotherapy (2500 rad [25 Gy] in 10 fractions in 2 weeks). En bloc resection was then performed. Postoperatively, depending on the surgical specimen findings, radiotherapy was given to a dose ranging from 5000 rad (50 Gy) in 5 weeks to 6000 rad (60 Gy) in 6 weeks equivalent continuous schedules. No residual tumor was found in 28% of the surgical specimens and only minimal tumor in 41%. A functionally intact limb was preserved in 30 patients (94%). Local recurrence developed in one patient (3%). The actuarial overall survival at three years was 70% and disease-free survival 57%.

Combination chemotherapy for metastatic carcinoma of the ampulla of Vater--report of three cases.

Three patients with metastatic carcinoma of the ampulla of Vater received celiac artery infusion of 5-fluorouracil, adriamycin, mitomycin-C, and streptozotocin followed by intravenous administration of the same combination. In two patients with measurable disease, one partial (6.0 months) and one complete response (16.0 + months) occurred. Two out of three patients remain alive at 30.0+ and 21.0+ months. Carcinoma of the ampulla of Vater may be a neoplasm responsive to combination chemotherapy.

Hepatic arterial chemotherapy and occlusion for palliation of primary hepatocellular and unknown primary neoplasms in the liver.

Eighteen patients with malignant liver disease were treated with hepatic arterial infusion (HAI) of floxuridine (FUDR), Adriamycin (doxorubicin), and mitomycin C (FUDRAM). Twelve of the patients had primary hepatocellular carcinoma and six had metastatic liver carcinoma originating from an unknown primary site. One complete remission and seven partial remissions (greater than or equal to 50% reduction in tumor size) were observed among 12 hepatocellular cancer patients, while only one partial remission was achieved among six patients with unknown primary liver neoplasms. When arterial occlusion was added to HAI of FUDRAM, a prolongation of median survival to 14 months as opposed to six months in patients with an intact arterial tree was observed (P = 0.02). Arterial occlusion had its effect on survival particularly among patients who failed to respond to HAI of FUDRAM. Thus, among nonresponding patients, the addition of arterial occlusion resulted in a median survival of 10.5 months while median survival in those without arterial occlusion was six months (P = 0.08). With procedure-related morbidity being minimal, we conclude that arterially administered FUDRAM offers a notable palliation to patients with primary hepatocellular carcinoma. In patients with unknown primary liver neoplasms and those with hepatocellular cancer who fail HAI of FUDRAM, arterial occlusion can offer additional palliation.

Constant infusion schedule for adriamycin: a phase I-II clinical trial of a 30-day schedule by ambulatory pump delivery system.

Eighteen patients received a continuous intravenous infusion of adriamycin for 14-60 days in a phase I study in which the dose rates were escalated from 2 mg/sq m/day to 5 mg/sq m/day to establish the optimal dose to be delivered over a 30-day period. The drug was delivered via a tunneled subclavian catheter by a portable infusion pump (Cormed model ML-6) primed to provide a volume of diluted drug of 10 cc/day. Leukopenia and stomatitis were observed at 4 mg/sq m/day doses or greater in 50% of courses. At doses less than 4 mg/sq m/day, only 3/17 courses (18%) were associated with stomatitis. Partial alopecia developed in all patients, but less than 50% of scalp hair was affected. The cumulative dose of continuous infusion adriamycin at 30 days is comparable to the dose delivered by standard bolus intermittent schedules (60-90 mg/sq m g 21 days), but the adverse drug effects are eliminated or substantially reduced. Cardiac toxicity was assessed in selected patients treated to 450 mg/sq m or greater by cardiac biopsy and/or gated pool studies. No histopathologic lesions were noted in 3 patients receiving 450 mg/sq m or greater. The recommended daily dose rate of adriamycin in this protracted infusion regimen is 3 mg/sq m/day. The phase II study of this schedule and dose rate in 38 additional patients (a total of 52 evaluable patients) demonstrated objective responses in 1/9 soft tissue sarcoma, 1/3 mesothelioma, 1/3 hepatoma, and 2/13 breast cancer. Phase III studies of the protracted continuous infusion schedule for adriamycin are indicated in that clinical activity is demonstrated at a substantial reduction in toxicity. Pharmacologic studies expanding the existing data base are also necessary.

Adriamycin therapy by continuous intravenous infusion in patients with metastatic breast cancer.

Patients with metastatic breast cancer previously treated with non-Adriamycin containing chemotherapy were treated with Adriamycin at a dose of 60 mg/m2 administered as a continuous infusion through a central venous catheter. The duration of Adriamycin infusion was escalated by 100% increments from 24-96 hours, but the majority of patients were maintained on 96-hour infusions. Thirteen of 27 patients achieved objective response (1 CR, 12 PR), six improved, and eight failed to respond to Adriamycin. Administration of Adriamycin by infusion led to a decrease in the severity of nausea and vomiting, but had no effect on myelosuppression and alopecia secondary to Adriamycin. The cardiac toxicity of Adriamycin was reduced in patients who received maintenance therapy with 96-hour infusions of Adriamycin.

Radical Resection of Malignant Bone and Soft Tissue Tumors

We described a case of osteosarcoma involving the proximal end of the humerus which was successfully treated by interscapulo-thoracic resection following preoperative arterial infusion of adriamycin, and another case of malignant fibrous histiocytoma involving the inguinal region which was treated by hemipelvic resection.Detailed investigation of tumor localization by computerized tomography and precise observation of preoperative arterial infusion of adriamycin is a useful method to determine indication for radical resection of malignant bone and soft tissue tumors.

Treatment of Osteosarcoma

Amputation for two cases and wide resection for a case of Osteosarcoma who were decreased tumor growth by preoperative intermittent arterial infusion of high dose adriamycin is described.It may be effective to prevention against pulmonary metastasis that high dose adriamycin infusion into the central vein or pulmonary artery.

Mathematical model for adriamycin (doxorubicin) pharmacokinetics.

Adriamycin (doxorubicin), an active antineoplastic drug, is rapidly distributed across cell membranes and is concentrated within cells. Binding to protein and to tissue readily occurs. The drug is metabolized to both fluorescent and nonfluorescent compounds, the liver being the main organ of biotransformation and elimination. A multicompartment, open model that accounts for these processes has been derived. The model assumes an initial volume of distribution of 60% of body weight and includes two peripheral adriamycin compartments and a subsystem for adriamycinol, a major metabolite. Plasma and urine concentrations of adriamycin and adriamycinol were determined for four patients treated with adriamycin (60 mg/m2), and these concentrations were used to calculate rate constants for the model. Concentrations were measured by fluorescence assay after thin-layer chromatographic separation of parent compound and metabolites. Differential equations were solved by the SAAM computer program. Evaluation of adriamcinol pharmacokinetics suggests that the previously reported high concentrations of adriamycinol immediately after IV infusion of adriamycin are an artifact of the fluorescence method and that observed plasma concentrations of adriamycinol are the sum of adriamycinol concentrations and approximately 10% of the adriamycin concentrations. Corrected peak plasma concentrations of adriamycinol occur 2--12 h after infusion of adriamycin.

Hepatic artery ligation and adriamycin infusion chemotherapy for hepatoma

Two patients with hepatoma of the liver were treated with ligation of the hepatic artery and continuous infusion of adriamycin into the distal arterial branch. Both patients had tumor replacing 60-75% of the normal liver parenchyma. There was clinical improvement and objective shrinkage of the tumor by liver scan lasting for 5 and 7 months. But both cases died 7 and 11 months later, probably of cardiac toxicity (total dose of adriamycin = 500 mg/m2).