melphalan and Leukopenia

Severe systemic toxicity and hemodynamic changes after isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF-alpha) and melphalan, with or without interferon-gamma, have been reported in several series. We studied whether these side effects could be precluded by preventing leakage from the isolated circuit into the systemic circulation.. Clinical and pharmacokinetic data for 20 consecutive patients with recurrent melanoma of the limbs who were treated by ILP with TNF-alpha (3-4 mg) and melphalan, with or without interferon-gamma, were studied. Leakage rates and TNF-alpha levels were determined during and after ILP and were correlated with systemic toxicity and hemodynamic changes.. Only two patients experienced leaks (2% and 13%) during ILP. For 18 patients without leakage, the mean peak systemic TNF-alpha level was 2.8 ng/ml at 10 minutes after ILP. After leakage, the peak systemic TNF-alpha levels were 31.9 and 88.3 ng/ml at 5 minutes. Toxicity was mild and consisted mainly of fever (n = 17) and nausea/vomiting (n = 19) during the first day after ILP. Some patients developed tachycardia (n = 6), hypotension (n = 3; responding immediately to fluid challenge), a decrease in the WBC count (n = 3; grade I) or thrombocyte count (n = 11; grade I/II, no hemorrhage or therapeutic intervention), or hepatotoxicity [cytolysis (n = 15; 14 grade I/II and 1 grade IV) or hyperbilirubinemia (n = 7; grade I/II, all resolving spontaneously)]. Patients with tachycardia or hepatotoxicity exhibited significantly higher TNF-alpha levels after ILP, compared with other patients.. Systemic toxicity after ILP with TNF-alpha is minimal and does not differ from that after ILP with melphalan alone when leakage is adequately controlled.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Humans; Hypotension; Interferon-gamma; Leukopenia; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Tachycardia; Thrombocytopenia; Tumor Necrosis Factor-alpha

Thirty-three patients with symptomatic Waldenström's macroglobulinemia have been treated with the M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Therapy was administered every 5 weeks for 2 years and every 10 weeks for an additional 1-3 years. Median clinical and laboratory parameters included age 70 years (range 52-87), performance status 1 (1-3), prior therapy 7, weight loss 12, symptomatic hyperviscosity 13, splenomegaly 22, lymphadenopathy 7, hemoglobin 9.6 g/dl (6.7-14.6), IgM paraprotein level 2000 mg% (340-11,600), and serum viscosity 2.1 (1.4-6.0). Responses were observed in 27 patients, of whom 21 were partial responses. Survival ranges from 1 to 120+ months with 58% of patients projected to be alive at 10 years. Twenty-one patients remain alive, of whom 10 are greater than or equal to 6 years from initiation of therapy with M-2. Treatment has been well tolerated with usually only mild to moderate hematologic toxicity. Median nadir white blood cells during the first cycle was 3000/mm3 (1000-5500). Peripheral neuropathy was seen in 54% secondary to vincristine. Nausea/vomiting, anemia requiring transfusions, and alopecia were each noted in approximately 25% of patients. Sepsis was observed in 2 patients. Two characteristics, age and prior therapy, were found to be of borderline statistical significance (p = 0.03) using univariate analysis but were not significant with multivariate analysis. The M-2 protocol may be able to produce prolonged survival in the majority of patients with Waldenström's macroglobulinemia. Additional trials are needed to develop recommendations for therapy as well as factors predictive for survival and suitability for treatment.

Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Drug Administration Schedule; Humans; Leukopenia; Melphalan; Nausea; Prednisone; Vincristine; Vomiting; Waldenstrom Macroglobulinemia

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Carmustine; Clinical Trials as Topic; Cyclophosphamide; Drug Administration Schedule; Female; Humans; Immunoglobulin A; Immunoglobulin D; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Peptichemio; Prednisone; Prognosis; Random Allocation; Vincristine

Between September 1976 and May 1980, 135 patients with operable breast cancer and positive axillary nodes received l-phenylalanine mustard, adjunct to surgery, 0.15 mg/kg for five days, six weekly, and were randomised prospectively to levamisole 150 mg for three days, two weekly, or a placebo. Treatment was continued for two years or until evidence of treatment failure, whichever was the sooner. At 4 1/2 years, for all patients, there was no significant difference between the two groups (P = 0.09), but in a subgroup of women less than or equal to 50 with 1-3 positive nodes, levamisole had a negative effect (P = 0.05). Although an analysis of the same age group, independent of the nodal status, did not reach significance, there was a trend in favor of placebo (P = 0.08) which was also apparent in premenopausal women (P = 0.15). In postmenopausal patients, however, and in those with more advanced disease with four or more positive nodes, although the results also failed to reach significance the trend in these subgroups favored levamisole. The results of this study suggest that levamisole has no place in the primary therapy of breast cancer in younger women and those with more favorable disease. The value of this agent in older patients and those with more advanced primary disease, remains unproven, but the favorable trends are in accord with a number of other studies with levamisole in metastatic breast and resectable lung cancer. Retrospective analysis confined to those women who received 75% or more of the total dose of l-phenylalanine mustard showed no evidence for a dose-responsive effect of adjuvant chemotherapy on the described pattern of results.

Topics: Age Factors; Breast Neoplasms; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leukopenia; Levamisole; Lymphatic Metastasis; Melphalan; Menopause; Middle Aged; Placebos; Retrospective Studies; Thrombocytopenia

From May 1978 until November 1980, 169 previously untreated patients with advanced epithelial ovarian cancer were entered into a prospective randomized clinical trial comparing the combination of hexamethylmelamine, Adriamycin, and cyclophosphamide (HAC) to a combination of melphalan and cis-platinum. Eleven patients were excluded from analysis and another 5 patients were excluded from response analysis. Of 153 patients evaluable for response, there were 47, or 30.7%, complete responders (all determined surgically), 6 partial responders, and 100 nonresponders. The response rate for the HAC group was 31% and for the melphalan-platinum group was 37.8%. The overall response rate was 34.6%. Residual tumor diameter (less than or greater than 2 cm) exerted a statistically significant effect on response--47.8 vs 24.4%. Of the 47 complete responders, 7, or 14.9%, have relapsed, with the median duration of remission of 44+ months. Of the 158 patients evaluable for survival, 90 patients have died, with a median survival time of 27.9 months (HAC = 26.4 months, melphalan-platinum = 29.6 months). Age, FIGO stage, histologic grade, and residual disease all exerted a significant effect on survival time. Second-line therapy in the treatment failures was of no benefit. Hematologic toxicity was greater in the melphalan-platinum group. Gastrointestinal toxicity was severe in both groups. Other toxicities were minor and infrequent.

Topics: Adult; Altretamine; Anemia; Antineoplastic Agents; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leukopenia; Melphalan; Middle Aged; Ovarian Neoplasms; Prospective Studies; Random Allocation; Thrombocytopenia

Two hundred ninety-three patients were randomly assigned to three treatment regimens following mastectomy for operable but prognostically unfavorable breast cancer: L-PAM, CFP, or CFP with radiation therapy. For premenopausal patients an increased risk of recurrence was associated with the presence of unfavorable local signs, large number of lymph nodes involved, greater body weight, younger age, and L-PAM treatment. For the postmenopausal patients only three factors were associated with an increased risk of recurrent disease: large tumor size, large number of lymph nodes involved, and inner/central location of the primary lesion. Specifically, the treatment employed has shown no effect. Of particular importance is the fact that for neither group of patients does our experience presently demonstrate clear association of recurrent disease with the level of drug dose administered. Furthermore, evidence suggests that although patients who experience little or no myelosuppression have significantly worse disease-free intervals than patients who experience moderate or severe myelosuppression, here is no benefit for severe myelosuppression over moderate, myelosuppression.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leukocyte Count; Leukopenia; Mastectomy; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Prednisone; Prognosis; Random Allocation; Thrombocytopenia

Sixty-five patients with multiple myeloma resistant to melphalan were randomized to receive cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP) (30 patients) or carmustine (BCNU), doxorubicin, and prednisone (BAP) (35 patients). Objective responses occurred in two patients in the CAP group and in seven in the BAP group. Indirect responses were noted in seven additional patients in the CAP group and in six additional patients in the BAP group. Toxic effects consisted mainly of leukopenia and thrombocytopenia. Median survival did not differ between the two treatment groups (CAP, 8.4 months; BAP, 7.7). Objective responders had a longer survival than nonresponders (14.5 vs 7.7 months).

Topics: Aged; Antineoplastic Agents; Carmustine; Cyclophosphamide; Doxorubicin; Drug Resistance; Drug Therapy, Combination; Female; Humans; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Random Allocation; Thrombocytopenia

The influence of renal insufficiency on melphalan-induced myelosuppression was examined during the initial 10 weeks of treatment in 295 patients with multiple myeloma. Patients were randomized to receive either oral melphalan (0.15 mg/kg/day for 7 days, followed by 0.05 mg/kg/day after recovery from the wbc count nadir) or iv melphalan (16 mg/m2 every 2 weeks for four doses, followed by a single dose every 4 weeks). All patients received a 6-week tapering course of prednisone. Patients with renal insufficiency (BUN greater than or equal to 30 mg/100 ml) had a significantly higher frequency of severe leukopenia (less than or equal to 1000 cells/mm3) following iv melphalan than did patients with normal renal function (50% vs 15%, respectively; P = 0.007). The latter effect resulted in an increased frequency of drug-related deaths secondary to infection. The frequency of severe thrombocytopenia (less than or equal to 25,000 cells/mm3) was also greater in patients with renal failure following iv melphalan therapy. Reduction of iv melphalan dose to 50% in patients with elevated BUN reduced the frequency of these complications to levels that were not significantly different from those observed in patients with normal renal function. The frequency of severe myelosuppression was independent of renal function in patients receiving oral melphalan. Possible explanations for these findings are discussed.

Topics: Blood Urea Nitrogen; Bone Marrow; Humans; Kidney; Kidney Diseases; Leukopenia; Melphalan; Multiple Myeloma; Random Allocation; Thrombocytopenia

A total of 361 evaluable patients with previously untreated multiple myeloma were randomized to receive oral melphalan (0.15 mg/kg/day for seven days, followed by 0.05 mg/kg/day after recovery from the nadir of the leukocytes), BCNU (150 mg/m2 intravenously every six weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-week course of prednisone starting at 0.8 mg/kg for the first two weeks. At week 22, one-half of the patients were randomized to receive vincristine (1 mg/m2) and prednisone (0.6 mg/kg for seven days) every two months in addition to previous therapy. The melphalan treated patients showed a significantly higher overall objective response frequency (59%), according to Myeloma Task Force criteria, when compared to those treated with BCNU (40%) or CCNU (42%). The survivals for all patients were not statistically different for the three treatment programs. However, the good-risk patients treated with melphalan had significantly longer survival (P = 0.02) than the equivalent patients who received BCNU or CCNU. The addition of vincristine and prednisone at week 2 did not significantly increase the percentage of subsequent objective responses or prolong the subsequent survival of any treatment group. It is concluded that oral melphalan is superior to BCNU and CCNU in producing objective responses and in prolonging survival in good risk patients.

Topics: Antineoplastic Agents; Carmustine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukopenia; Lomustine; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Random Allocation; Thrombocytopenia; Vincristine

Two hundred fifty-two previously untreated evaluable patients with multiple myeloma were entered into a study testing a regimen of three intravenous alkylating agents, melphalan, cyclophosphamide, and carmustine (BCNU), given in combination (BCMP) against a regimen employing oral melphalan (MP). Both regimens included a tapering course of prednisone. Objective responses based on the Myeloma Task Force criteria were significantly more frequent in the group receiving BCMP. Survival for the entire group of BCMP-treated patients was not significantly better than that for MP-treated patients (p = 0.62). However, when the survival of the poor-risk (high tumor cell load) group of patients treated with BCMP was compared with the survival of the poor-risk (high tumor cell load) group of patients treated with MP, an improvement in survival attributable to BCMP therapy was seen (p = 0.049 and 0.02, respectively). In the good-risk (low and intermediate tumor cell load) group, BCMP treatment resulted in a trend toward poorer survival, but this did not achieve statistical significance (p = 0.080 and 0.23, respectively). These results indicate that optimal therapy in myeloma may be dependent on the extent of disease at the time of first treatment. Additional studies to explore the effects of treatment intensity and duration are needed in order to design improved myeloma treatment based on the patient's extent of disease.

Topics: Alkylating Agents; Carmustine; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukopenia; Melphalan; Multiple Myeloma; Prednisone; Prognosis

Topics: Adenocarcinoma, Mucinous; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leukopenia; Lymphatic Metastasis; Mastectomy; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prospective Studies; Thrombocytopenia

Topics: Anemia, Aplastic; Clinical Trials as Topic; Cyclophosphamide; Drug Combinations; Evaluation Studies as Topic; Humans; Leukopenia; Melphalan; Middle Aged; Multiple Myeloma; Palliative Care; Prospective Studies; Radiography, Thoracic; Retrospective Studies; Thrombocytopenia

Topics: Clinical Trials as Topic; Cyclophosphamide; Hematopoiesis; Humans; Leukopenia; Melphalan; Neoplasms; Thrombocytopenia

Intermittent courses of melphalan and prednisone is still the standard chemotherapy for the initial treatment of multiple myeloma (MM) in patients who cannot undergo high-dose chemotherapy/radiotherapy with either allogeneic or autologous stem cell transplantation. However, the absorption of the drug from the gastrointestinal tract is highly variable from patient to patient and therefore, different plasma levels of the drug are reached in the blood of individual MM patients. In order to overcome this limitation we decided to use intermediate dose (15-30 mg/m2, day 1) intravenous melphalan in resistant or relapsing MM patients as well as in untreated patients not eligible for a more aggressive protocol. Moreover, considering the good results obtained by other investigators using dexamethasone alone or associated with interferon in the treatment of resistant or relapsing MM patients, dexamethasone (40 mg total dose, day 1) and the lymphoblastoid alpha interferon (3 MU, 3 times a week x 3 weeks, from day 8 to day 26 of each course) were added to intravenous melphalan. Courses were repeated every 5 weeks for a total of 6 cycles. We treated 62 MM patients obtaining a response (defined as reduction > 25% of the initial monoclonal component value associated with disappearance of the clinical symptoms) in 38 out 62 evaluable patients (61%) and stable disease (defined as a decrease of < 25% in the base-line serum monoclonal component level with disappearance of all symptoms present at diagnosis) in 9 (14.5%) more patients. The overall median response duration was 14 months and the overall median survival duration (from the time of inclusion in this protocol) for the 62 patients entered into the study was 34 months. No severe (Grade 3-4 of the WHO) hematological as well as non hematological toxicities were observed. This lack of severe toxicity allowed us to administer the drugs on an outpatient basis. In conclusion, the overall response and the low grade of toxicity in this category of patients are encouraging and suggest that this protocol is both effective and safe treatment for high risk MM patients.

Topics: Actuarial Analysis; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Dexamethasone; Disease-Free Survival; Drug Evaluation; Drug Resistance; Drug Therapy, Combination; Female; Humans; Interferon-alpha; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Recurrence; Risk Factors; Sepsis; Survival Rate; Thrombocytopenia; Treatment Outcome

Time-related changes in apoptotic leukocyte numbers were studied in peripheral blood sampled from 12 cancer patients before and after myeloablative chemotherapy (MC); six of them received hemopoietic cell grafts. Apoptotic leukocytes were counted in fresh and ex vivo incubated blood samples. Nuclear chromatin autolysis was registered in supravital Acridin Orange-stained granulocytes and lymphocytes. The levels of apoptosis in fresh peripheral blood were under 1.5%. Incubation for another 3 h revealed considerable numbers of apoptosis-prone leukocytes both in untreated patients and healthy donors. High-dose chemotherapy with busulphan, cyclophosphamide or alkeran was followed by a sharp increase in apoptotic cell counts which peaked on days 7-9, before leukopenia started on days 13-15 at the earliest. It is suggested that apoptosis of mature leukocytes is a major cause of leukopenia development induced by chemotherapy. The simple technique of apoptosis-prone cell detection in whole blood may be effectively used in serial screening of hematological side-effects of chemotherapy.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Busulfan; Cyclophosphamide; Humans; Leukocytes; Leukopenia; Melphalan; Neoplasms

A 29-year-old woman, with a slightly elevated temperature for 3 weeks, increasing dyspnoea at rest, markedly reduced general condition and in heart failure, was found to have a leucocytosis of 100,000/microliters, anaemia (haemoglobin 6.3 g/dl) and thrombocytopenia (41,000/microliters). There were 62% plasma cells in the blood smear. Immunoelectrophoresis of serum and urine revealed kappa-light chains and immunocytology demonstrated IgG-kappa. There was no radiological evidence of osteolysis, while ultrasound examination showed multiple abdominal lymphomas and marked hepatosplenomegaly. Bone marrow smear showed a 90% infiltration of plasma cells. High-dosage melphalan treatment (single intravenous injection of 140 mg/m2) resulted in complete remission after myelodepression over several weeks. Two extramedullary recurrences 5 and 12 months after the diagnosis had been made were successfully treated with high-dosage melphalan, but it was associated with severe and long-lasting myelodepression. Septicaemia with renal and hepatic failure developed and the patient died 6 weeks after the third course of high-dosage melphalan, 14 months after the diagnosis.

Topics: Acute Disease; Adult; Bone Marrow Examination; Cell Count; Female; Humans; Immunoglobulin Light Chains; Leukemia, Plasma Cell; Leukopenia; Melphalan; Plasma Cells; Thrombocytopenia

Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I-II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0 X 10(6) IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table. Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Drug Synergism; Female; Humans; Interferon Type I; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Myocardial Infarction; Prednisone; Sepsis

We have previously reported that chloroethyl nitrosourea and nitrogen mustard bone marrow toxicity can be selectively reduced by placement of the cytotoxic group on specific positions of a glucose molecule. We have now synthesized and evaluated a new drug in which the mustard cytotoxic group is attached to the carbon-6 position of galactose (C6-GLM). C6-GLM, administered i.p. as a single 10% lethal dose of 15.5 mg/kg, produced a 121% increase in life span (ILS) in mice bearing the ascitic P388 leukemia, compared to a 60% ILS with a 10% lethal dose of nitrogen mustard (P less than 0.01). A single p.o. dose of C6-GLM, 16 mg/kg, produced an ILS of 58%. Against i.p.-implanted B-16 melanoma, i.p. C6-GLM produced a 56% ILS compared to 30% with an equitoxic dose of nitrogen mustard (P less than 0.01). The activity of the two drugs for Ehrlich ascites was comparable, with 60% survivors with the galactose mustard. A single 10% lethal dose of C6-GLM reduced the white blood cells to 74% of control; circulating granulocytes remained at 91% of initial values. With nitrogen mustard, the nadir white blood cell count was 57% of control with an absolute granulocyte count of 70% of initial values (P less than 0.01). The toxicity of melphalan was considerably greater, with a lower and more protracted while blood cell nadir and an absolute neutrophil count nadir of 49% of control. These findings paralleled the relative decrements in bone marrow DNA synthesis produced by the three drugs. Measurement of human bone marrow granulocyte-macrophage colony-forming units, following in vitro exposure to graded concentrations of the three mustards, confirmed the bone marrow sparing properties of C6-GLM. At the highest concentration, 1 X 10(-2) mM, the latter drug produced only a 33% reduction in colonies compared to a 75% reduction with nitrogen mustard and a virtual elimination of activity of colony-forming units with melphalan. The demonstration of antitumor activity, at least equivalent to nitrogen mustard, without the necessity of significant bone marrow toxicity supports the development of C6-GLM for clinical trials in humans.

Topics: Animals; Bone Marrow; DNA Replication; Drug Evaluation, Preclinical; Female; Galactosamine; Hematopoietic Stem Cells; Leukemia P388; Leukemia, Experimental; Leukopenia; Male; Mechlorethamine; Melphalan; Mice; Mice, Inbred DBA; Neutrophils; Structure-Activity Relationship

Peptichemio (PTC), a multipeptidic complex of m-L-phenyl-alanine mustard, was administered to 39 children with neuroblastoma at relapse. The compound was given in two 5-day cycles at dosages varying from 1.0-1.5 mg/kg/day. We were able to evaluate 29 of the initial 39 children for PTC effect; 21 of them had received PTC as first therapy following diagnosis. Ten patients underwent other chemotherapy for relapse before PTC. Three patients were off therapy when relapse occurred. Subjective improvement was observed in 18 cases (62%). Eleven patients (38%) experienced an objective regression, which was scored as complete response in three cases, partial response in two, mixed response in six. In ten children no significant disease change was observed; the remaining eight had a progression of their disease while receiving PTC. The incidence of responses has been higher in patients off therapy at moment of relapse, and lower in those pretreated for their relapse. Previous administration of PTC did not reduce the chance of response at relapse. Major toxic effects were transient, mostly moderate myelodepression and phlebosclerosis. Allergic reactions, nausea, and vomiting, occurred in a few patients. These data indicate that PTC may exert objective antitumor activity in approximately one-third of neuroblastoma patients at relapse.

Topics: Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Leukopenia; Male; Melphalan; Neuroblastoma; Peptichemio; Recurrence; Thrombocytopenia; Veins

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Vincristine

The results achieved with different approaches of chemotherapy protocols applied to 81 patients affected by multiple mieloma and followed up for a duration of 16 years in the geographical area pertaining to the Saronno County Hospital are presented. All the patients are divided into sub-groups, according to the type of treatment they required while being monitored over the years. Each single sub-group is evaluated according to the following criteria: objective response to therapy; median survival rates; toxic effects due to drug exposure. The results are analyzed with reference to the most relevant literature on the matter. A comprehensive retrospective review of emerging data suggests an overlapping median survival--30 and 31 months--in patients given monochemotherapy as such as in those given polychemotherapy. Evidence is also made for a clearly meaningful increase of survival in treated patients compared with that of untreated ones. Median survival depends significantly on the initial stage of the disease. Both therapeutical effectiveness and toxicity are shown to be higher, in accordance with the current literature, in polychemotherapy which include vincristine--especially when a large tumor cell mass is pointed out--compared with therapy based on alkilating agents and prednisone.

Topics: Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Prognosis; Thrombocytopenia; Vincristine

Misonidazole (MISO) given as a large single dose enhanced the action of cyclophosphamide (Cy) and melphalan (L-PAM) in two mouse tumours. Below a dose of about 500 mg kg-1 it had no chemosensitizing effect. When MISO was given as a series of small doses by repeat injection over an 8 h period, in order to stimulate human pharmacokinetics, it significantly enhanced the action of Cy in the SA F tumour. It also enhanced the action of Cy and L-PAM in the WHFIB tumour as assayed by tumour cell survival in vitro following treatment in vivo but not when the assay was tumour growth delay. There was no enhancement by MISO of the leukopenia due to Cy or L-PAM. The results suggest that, in some tumours there may be benefit from the combination of clinically relevant MISO doses with alkylating agents. The leucopenia induced by these agents should not be enhanced by the MISO.

Topics: Animals; Cell Survival; Cyclophosphamide; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Leukopenia; Melphalan; Mice; Mice, Inbred Strains; Misonidazole; Nitroimidazoles; Sarcoma, Experimental; Time Factors

Topics: Amifostine; Animals; Cell Survival; Cyclophosphamide; Drug Therapy, Combination; Leukopenia; Melphalan; Mice; Mice, Inbred Strains; Misonidazole; Nitroimidazoles; Organothiophosphorus Compounds; Sarcoma, Experimental

A combination of AMSA and peptichemio was evaluated in patients with advanced breast cancer refractory to conventional chemotherapy. Of 33 evaluable patients, five patients (15%) achieved partial remission, two patients (6%) had less-than-partial remission, nine patients (27%) had stable disease, and seventeen patients (52%) had progressive disease. The median duration of response was 6 months (range: 3-8 months). The median duration of stable disease was 5 months (range: 2-7 months). Myelosuppression was the dose-limiting toxicity. This combination of AMSA and peptichemio did not result in an improved response rate or duration of remission compared to the previous experience with single-agent therapy with either of these agents.

Topics: Adult; Aged; Aminoacridines; Amsacrine; Antineoplastic Agents; Breast Neoplasms; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leukopenia; Melphalan; Middle Aged; Neoplasm Metastasis; Peptichemio; Thrombocytopenia

From January 1975 to May 1981, 25 consecutive patients with multiple myeloma (MM) were entered in a prospective study and treated with the M-2 protocol (melphalan, prednisone, cyclophosphamide, vincristine, and carmustine [BCNU]). The Karnofsky performance status was less than 70 in 62% of the patients. Nineteen patients were classified as being in stage III, three were in stage II, and three were in stage I. All patients had symptomatic and previously untreated MM. In 17 of 21 (80.9%) evaluable patients, an objective response according to Myeloma Task Force criteria was obtained. There was no difference in response rate among patients in the various stages of the disease or according to types of proteins secreted. The median time to obtain an objective response was 2 months and the median duration of the remission is 18+ months. The actuarial median survival was 42 months. In the first 15 months of follow-up, 20% of the patients died. Toxicity was not negligible and was mainly hematologic. One treatment-related death occurred. Our study confirms the efficacy of the M-2 protocol in MM and supports the data reported by the Memorial Hospital group.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Prospective Studies; Thrombocytopenia; Vincristine

Topics: Adenocarcinoma; Female; Fluorouracil; Gastroenteritis; Humans; Leukopenia; Melphalan; Middle Aged; Peptichemio; Sigmoid Neoplasms

Topics: Humans; Injections, Intravenous; Leukopenia; Melphalan; Metabolic Clearance Rate; Multiple Myeloma; Thrombocytopenia

Leukopenia and thrombocytopenia were studied after loading doses of melphalan (5 mg/daily for 18-25 days) in 71 myeloma patients. Seventy per cent of the patients developed pronounced leukopenia (white cells less than 2.0 X 10(9)/l) and/or thrombocytopenia (platelets less than 100 X 10(9)/l). The patients with pronounced and moderate hematological side-effects, respectively, were compared for weight and age. The body weight was the same in the two groups, indicating that the patient's weight is of minor importance for the dosage of melphalan. There was a numerical difference in age, on the borderline for statistical significance, indicating that the age of the myeloma patient may be of minor importance for the dosage of melphalan. It is possible that more pronounced age differences may be of greater importance in this respect. Fifteen patients with myeloma were treated with cyclophosphamide. Compared with melphalan, the effect on white cells was the smae, while the incidence of thrombocytopenia was statistically significantly lower with cyclophosphamide.

Topics: Aged; Bone Marrow; Cyclophosphamide; Humans; Leukopenia; Melphalan; Middle Aged; Multiple Myeloma; Thrombocytopenia

Immunoblastic lymphadenopathy is a recently described lymphoproliferative disorder, presumably of B-cell origin. It is characterized by regional or generalized lymphadenopathy, usually associated with hypergammaglobulinemia or dysproteinemia. Other findings may be hepatosplenomegaly, dermatitis, fever, malaise, weight loss, and various altered immunologic reactions. Histologically, the involved lymph nodes show immunoblast, plasmacytoid, and plasma cell proliferation. This may be extranodal as well. The case reported here is one of the few followed up prospectively. The patient's purpuric eruption was an apparent manifestation of a type II mixed cryoglobulinemia. Differing from what has usually been reported, we noted hypogammaglobulinemia and findings in part of altered cell-mediated immunity. Despite leukopenia and anemia there were no infectious episodes. Although a satisfactory treatment regimen has not been established, there was beneficial response to prednisone and short courses of melphalan.

Topics: Allopurinol; Anemia; B-Lymphocytes; Cryoglobulins; Female; Humans; Leukopenia; Lymphatic Diseases; Melphalan; Middle Aged; Paraproteinemias; Prednisone; Purpura, Hyperglobulinemic

A 41-year-old woman, presenting with renal failure, renal glucosuria and moderate anemia, was found to have light chain myeloma, indicated by a kappa chain M-component in the serum, heavy urinary excretion of kappa chains and plasma cell infiltration of the bone marrow. After administration of one course of melphalan, resulting in transient pancytopenia, the light chains disappeared completely, renal function returned to normal, glucosuria disappeared and the Hb concentration normalized. During an observation period of six years she has remained in good health and there has been no sign of relapse.

Topics: Adult; Female; Glycosuria; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Kidney Diseases; Leukopenia; Melphalan; Multiple Myeloma; Remission, Spontaneous; Time Factors

A four-drug adjuvant chemotherapy regimen (CONPADRI-I) was utilized in the primary treatment of 18 children with osteogenic sarcoma. All patients had surgical amputation for the primary lesion. The children then received cyclophosphamide, vincristine, melphalan, and adriamycin in defined combinations intermittently over a 72-week period. Of the 18 patients, 10 (55%) remain free of disease 24 months or longer from time of amputation.

Topics: Adolescent; Adult; Amputation, Surgical; Antineoplastic Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Heart; Humans; Leukopenia; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Thrombocytopenia; Vincristine

Topics: Afibrinogenemia; Animals; Antifibrinolytic Agents; Blood Cell Count; Blood Platelets; Chromium Radioisotopes; Coagulase; Cyclohexanecarboxylic Acids; Dogs; Female; Fibrinogen; Hematocrit; Immune Sera; Iodine Radioisotopes; Leukocyte Count; Leukopenia; Male; Melphalan; Oxygen; Partial Pressure; Pulmonary Embolism; Rabbits; Respiratory Insufficiency; Thrombin; Thrombocytopenia

Topics: Adult; Antineoplastic Agents; Cell Survival; Cyclophosphamide; Depression, Chemical; Etiocholanolone; Female; Fluorouracil; Humans; Injections, Intramuscular; Leukocyte Count; Leukocytes; Leukopenia; Male; Melphalan; Neoplasms; Stimulation, Chemical

Topics: Blood Cell Count; Blood Platelets; Drug Combinations; Humans; Leukocyte Count; Leukopenia; Melphalan; Plasmacytoma; Prednisolone; Prednisone; Thrombocytopenia

Topics: Adolescent; Aged; Bone Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Neoplasms; Ovarian Neoplasms; Sarcoma, Ewing; Testicular Neoplasms; Thrombocytopenia; Tonsillar Neoplasms; Uterine Neoplasms

Topics: Adolescent; Adult; Bone Marrow; Child; Child, Preschool; Dosage Forms; Female; Humans; Injections, Intravenous; Leukopenia; Male; Melphalan; Neoplasm Metastasis; Osteosarcoma; Thrombocytopenia; Time Factors

Topics: Humans; Leukopenia; Melphalan; Multiple Myeloma; Thrombocytopenia

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Child; Extremities; Female; Hemorrhage; Humans; Hypotension; Leukopenia; Lymph Node Excision; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Methods; Middle Aged; Postoperative Complications; Sarcoma; Skin Neoplasms

Topics: Anemia; Fluorouracil; Humans; Leukopenia; Melphalan; Nitrogen Mustard Compounds; Stomach Neoplasms; Thiotepa; Thrombocytopenia

Topics: Adolescent; Adult; Aged; Anemia; Cardiomyopathies; Chemotherapy, Cancer, Regional Perfusion; Child; Cyclophosphamide; Electrocardiography; Humans; Leg; Leukopenia; Melphalan; Middle Aged; Neoplasms; Tachycardia; Thiotepa; Vascular Diseases

Topics: Animals; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Female; Leukopenia; Lung Neoplasms; Lymphoma, Non-Hodgkin; Melphalan; Mice; Neoplasm Metastasis; Ovarian Neoplasms; Peritoneal Neoplasms; Rats; Sarcoma 180; Sarcoma, Experimental; Thiotepa; Triazines

Topics: Aged; Anemia, Sideroblastic; Blood Platelets; Female; Hemoglobinometry; Humans; Leukocyte Count; Leukopenia; Male; Melphalan; Polycythemia Vera; Primary Myelofibrosis

Topics: Adolescent; Adult; Dysgerminoma; Humans; Leukopenia; Lung Neoplasms; Lymphatic Metastasis; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Teratoma; Testicular Neoplasms; Vinblastine

Topics: Blood Cell Count; Humans; Leukopenia; Melphalan; Multiple Myeloma; Thrombocytopenia

Topics: Humans; Leukopenia; Melphalan; Polycythemia Vera; Splenomegaly; Thrombocytopenia

Topics: Adult; Aged; Bence Jones Protein; Blood Protein Electrophoresis; Female; Humans; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Prognosis

Topics: Bence Jones Protein; Blood Cell Count; Bone Marrow; Electrophoresis; Humans; Leukocyte Count; Leukopenia; Melphalan; Multiple Myeloma; Thrombocytopenia

Topics: Anemia; Blood Protein Disorders; Chlorambucil; Humans; Hypercalcemia; Leukopenia; Melphalan; Plasmacytoma; Thrombocytopenia

Topics: Anemia; Cyclophosphamide; Humans; Leukopenia; Melphalan; Multiple Myeloma; Prednisone; Urethane

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bacteria; Chemistry Techniques, Analytical; Guinea Pigs; Leukocytes; Leukocytosis; Leukopenia; Melphalan; Mice; Phosphines; Polarography; Rabbits; Rats; Streptomyces

Objective improvement after therapy with melphalan occurred in all patients producing only Bence Jones kappa proteins, in half of the patients with myeloma serum proteins, and in none of those producing only Bence Jones lambda proteins.

Topics: Bence Jones Protein; Blood Proteins; Drug Therapy; Humans; Leukopenia; Melphalan; Multiple Myeloma; Myeloma Proteins; Neoplasms; Prognosis; Toxicology

Topics: Albuminuria; Blood Protein Electrophoresis; Humans; Leukocyte Disorders; Leukopenia; Mechlorethamine; Melphalan; Multiple Myeloma; Neoplasms; Thrombocytopenia

Topics: Geriatrics; Hodgkin Disease; Iatrogenic Disease; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Neoplasms; Radiography, Thoracic; Sarcoma; Thrombocytopenia; Toxicology

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Carcinoma, Krebs 2; Feeding and Eating Disorders; Leukopenia; Melanoma; Melphalan; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Sarcoma; Sarcoma, Experimental

Topics: Brain; Leukopenia; Melphalan; Mice; Neoplasms; Pharmacology; Rabbits; Rats; Research; Sarcoma; Sarcoma, Experimental; Tissue Extracts