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At least 19 recordsLinked to original sources
PubMed1980

Effect of peptichemio and of peptichemio plus hydrocortisone on growth and alkaline phosphatase activity in HeLa cells in vitro.

The actions of Hydrocortisone, Peptichemio and of Peptichmio + Hydrocortisone mixture in HeLa cells have been experimented. The results show an increase of cell number in the controls and a lower, but not statistically different growth, in the Hydrocortisone-treated cultures. In the cultures treated with peptichemio the growth is hardly evident, in the ones treated with the Hydrocortisone + Peptichemio mixture, the cell number is decreasing with time. ALP activity in cells treated with drugs is much higher than in the controls ones. The results either on cellular growth and on ALP activity, are compared to the Ara C ones. No significant difference in media ALP activity between drug-treated cultures and controls is evidentiated. The results show in the Peptichemio + Hydrocortisone mixture, that the action of Hydrocortisone is overcome by the Peptichemio one. By the cytochemical technique the enzyme localization is particularly evident in the cytoplasmic inclusions, which are very numerous in the cells treated with Peptichemio.

Alkaline Phosphatase↗
PubMed1982

Peptichemio versus melphalan (L-PAM) in advanced breast cancer.

Peptichemio is a polypeptide complex of L-phenylalanine mustard. Because of structural similarities between melphalan (L-PAM) and Peptichemio a prospective randomized study was done to compare the therapeutic efficacy of these two agents. After failing various combinations of doxorubicin, cyclophosphamide, fluorouracil, methotrexate, and vincristine patients with advanced breast cancer were randomized to receive either Peptichemio or L-PAM. Peptichemio was administered at 75-100 mg/m2 and L-PAM at 30-40 mg/m2 IV q 3-4 week interval. Of 56 evaluable patients, 28 received peptichemio and 28 received L-PAM. There were no objective responses in the L-PAM group, and disease stabilized in four patients (14%). The median duration of stable disease was three months (range, 3-4 months). In the peptichemio group seven patients (25%) achieved a partial remission, one patient (3%) achieved less than partial remission and three patients (11%) had stable disease. The median duration of response was six months (range, 5-7+ months) for responding patients and three months (range, 2-5 months) for stable disease. The major toxicity of both drugs was myelosuppression which was cumulative. In conclusion, peptichemio is an active agent in advanced breast cancer, but L-PAM is ineffective in previously treated patients with metastatic breast cancer.

Adult↗
PubMedDate not supplied

Increased toxicity and DNA cross-linking by peptide bound m-L-sarcolysin (Peptichemio) as compared to melphalan and m-L-sarcolysin in human melanoma cell lines.

Alteration of the melphalan molecule by shifting the di(2-choroethyl)aminogroup from the para- to the meta-position of the phenylalanine residue results in m-L-sarcolysin. By covalent conjugation of different amino acids at the amino- and carboxylgroups of this molecule, a mixture of six peptides known as Peptichemio has been synthesized. In a previous investigation we found that Peptichemio was less toxic to human lymphoblasts than m-L-sarcolysin. In contrast, in the present investigation we found that Peptichemio has higher cytotoxic effect than m-L-sarcolysin on two human melanoma cell lines. The higher cytotoxicity was paralleled by a higher induction of DNA cross-links by Peptichemio as compared to m-L-sarcolysin. A comparative analysis of the six peptides on Peptichemio showed differences in cytotoxic effects on a melanoma cell line. One of the six peptides displayed a considerably higher cytotoxicity than peptichemio itself.

Cell Line↗
PubMed1983

Inhibition of T and B lymphoblastic response by mithramycin, dacarbazine, prospidium chloride and peptichemio.

Four different cytostatic compounds (prospidium chloride, peptichemio, dacarbazine and mithramycin) have been assayed for their effect on lymphoblastic transformation of spleen cells from mice. The drugs did not affect cell viability at concentrations lower than 0.1-0.2 micrograms/ml (peptichemio and mithramycin) or than 10-20 micrometers/ml (prospidium chloride and dacarbazine). Except for peptichemio, which did not show any marked effect, these cytostatics acted more actively on B cells than on T cells at concentrations of drug not affecting lymphocyte viability. Mithramycin was the most active inhibitor of the mitogen-induced DNA synthesis in the cell. Concentrations of this drug to inhibit the blastogenic response to 50% (IC50) were lower than 0.1 microgram/ml. Inhibition of mitogenesis was less pronounced in the case of dacarbazine (IC50 = 50 and 10 micrograms/ml for T and B cells, respectively), prospidium chloride (IC50 greater than 50 and 50 micrograms/ml for T and B cells) and peptichemio (IC50 = 0.25 and 0.5 microgram/ml for T and B cells, respectively.

Animals↗
PubMed1984

Combination chemotherapy of metastatic breast carcinoma with cyclophosphamide, adriamycin, and peptichemio.

Thirty patients with metastatic carcinoma of the breast were treated with a combination of cyclophosphamide, Adriamycin (doxorubicin), and peptichemio (CAP) as an induction regimen, and maintenance regimen consisting of thiotepa, methotrexate, and 5-fluorouracil (TMF). Twenty-four patients were evaluable. Thirteen patients achieved an objective response for a response rate of 54.0% (complete remission plus partial remission). Median duration of response was 9.5 months (0-32+). The CAP regimen had severe myelotoxicity that led to dose reductions in 67% of patients. Furthermore, 50% of the patients required delay (greater than 28-day interval) in chemotherapy courses because of myelosuppression, and peptichemio had to be discontinued in seven patients. The CAP chemotherapy as an induction regimen for metastatic breast carcinoma resulted in underutilization of Adriamycin, and proved to be inferior to other Adriamycin-containing regimens. Although peptichemio used as a single agent had significant activity against breast cancer, it was not suitable for prolonged use in conjunction with other myelosuppressive agents. However, it may have a role in second-line therapy of metastatic breast cancer in conjunction with nonmyelosuppressive agents. The authors were unable to test the efficacy of non-cross-resistant maintenance therapy with TMF in this trial.

Adult↗
PubMed1987

Differential DNA cross-linking and cytotoxicity in PHA-stimulated human lymphocytes exposed to melphalan, m-L-sarcolysin and peptichemio.

DNA interstrand, as well as DNA protein cross-linking, was more efficient in phytohaemagglutinin-stimulated human lymphocytes exposed to m-L-sarcolysin as compared to melphalan at equivalent concentrations of the drug. The cellular uptake of m-L-sarcolysin was more efficient as compared to melphalan. With peptichemio, a mixture of 6 peptides containing m-L-sarcolysin, an intermediate level of DNA cross-linking was found. The differences in DNA cross-linking between the 3 drugs were parallel to differences in cytotoxicity. Peptichemio has been ascribed anti-metabolic properties in addition to the alkylating properties conferred by its m-L-sarcolysin content. In the phytohaemagglutinin-stimulated lymphocytes, however, the effect of peptichemio seems linked to its capacity for DNA cross-linking.

Cell Survival↗
PubMed1987

Intermittent pelvic arterial infusion with peptichemio, doxorubicin, and cisplatin for locally advanced and recurrent carcinoma of the uterine cervix.

The preliminary results of intraarterial chemotherapy with peptichemio, doxorubicin, and cisplatin as part of a multimodality treatment in locally advanced and recurrent cervical carcinomas are reported. Treatment consisted of a bilateral sequential infusion of peptichemio 20 mg, doxorubicin 10 mg and cisplatin 20 mg in a 6-hour period via an external infusion pump. After a rest period of 4 days, treatment restarted until maximum response or toxicity. Twenty-five patients, 12 with primary advanced (four Stage IIb, eight Stage III) and 13 with recurrent tumors were treated. All previously untreated patients obtained objective response. In particular, two patients with Stage IIb and III disease, respectively, achieved a complete response. Nine of 13 patients with recurrent disease (69%) were responsive, too, and therefore an overall objective response rate of 84% was achieved. Responses were noted after a median of five cycles of chemotherapy, whereas hematologic toxicity observed in all but one patient, was encountered after a median of four cycles. Toxicity of grade 1 and 2 was noted in 19 patients (76%), whereas of grade 3 and 4 in only 5 (20%). One treatment-related death, due to sepsis during myelosuppression, was reported. Catheter-related toxicity was noted in four patients causing femoral thrombosis in two. In one case a bypass operation was required. After intraarterial chemotherapy, all 21 responsive patients were eligible for radical surgery and 18 (86%) underwent both surgery and postoperative radiation therapy. Surgery was excluded in three patients. In these three cases radiation therapy alone was employed. In this series, the schedule of intraarterial chemotherapy employed was very effective. Patient accrual is ongoing in order to confirm the response rate so far obtained and to evaluate, with a longer follow-up, the impact of this multidisciplinary approach on local control and survival.

Adult↗
PubMed1982

Peptichemio induction therapy in myelomatosis.

Fifteen patients with multiple myeloma, two of whom had plasma cell leukemia, were treated between May 1974 and December 1978. Peptichemio was administered intravenously at doses of 40-80 mg/48 h, courses including 4-17 administrations in association with moderate doses of prednisone (15-50 mg/day) and androstanes at high dosages (250 mg weekly). In two patients PTC was associated with vincristine (VCR) administered on the first day of the course. Eight patients were previously untreated, four had been resistant to melphalan (MPH) and/or cyclophosphamide (CTX), and three had been treated irregularly with one or both of these alkylating agents. The criteria of response to therapy are reported. Out of a total of 15 PTC courses administered we obtained 13 responses, eight complete and five partial; no response was achieved in the other two patients. In the four patients who were resistant to MPH and/or CTX we obtained three responses, which were maintained with the same alkylating agent to which they had been resistant previously. The time needed to obtain a response in 90% of the patients was 6 weeks. Peptichemio was shown to be effective in patients in an advanced stage of the disease, in patients with light-chain myeloma and in those with plasma cell leukemia. The association of VCR potentiated the antitumor effect, but also increased the myelotoxicity. The PTC treatment was well tolerated. It is suggested that PTC be used in induction treatment of myelomatosis and in patients resistant to traditional alkylating agents.

Adult↗
PubMed1982

AMSA and peptichemio in the treatment of advances metastatic breast cancer: a phase II study.

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.

Adult↗
PubMed1975

Influence of cytotoxic drugs on platelet functions in vitro. III. Peptichemio.

The influence of Peptichemio (m-dichloroethyl-amino-l-phenyl-alanyl-peptide complex) on the following platelet functions was studied: aggregation, release of platelet factor 4, availability of platelet factor 3, acid phosphatases and reptilase clot retraction. Concentrations of the drug corresponding to that found in plasma of treated patients did not significantly influence platelet functions. Concentrations 10 times higher brought about an inhibition. It is concluded that after current dosage of Peptichemio, bleeding disorders caused by impairement of platelet functions are improbable.

Acid Phosphatase↗
PubMed1992

Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma.

PURPOSE: The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma. PATIENTS AND METHODS: From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT). RESULTS: Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5). CONCLUSION: Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.

Adolescent↗
PubMedDate not supplied

High dose peptichemio in pretreated neuroblastoma.

The aim of this study was to evaluate the antitumor effect and toxicity of a single course of Peptichemio at high dose (450 mg/sq m) given to children with neuroblastoma resistant to first line treatment or at relapse. A total of 28 children were treated. Seven children showed partial response, 4 minor response, 8 had stable disease, and in 8 the tumor progressed. The principal toxic effect was myelosuppression. Hemorrhagic enteritis with liver failure and toxic death occurred in 1 patient. High dose Peptichemio can be administered with tolerable toxicity, inducing tumor regression in one third of previously treated patients.

Adolescent↗
PubMedDate not supplied

Alternating intravenous courses of melphalan and peptichemio in high-risk multiple myeloma (preliminary results).

Six patients with high-risk multiple myeloma and one patient with primary amyloidosis were treated with a melphalan-peptichemio-prednisone association (PMP). The response trend seems promising, also in view of the low regimen bone marrow toxicity, but further studies could better evaluate the optimal PMP scheduling and peptichemio side effects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Rate of M-component changes and plasma cell labeling index in 25 patients with multiple myeloma treated with peptichemio.

Twenty-five consecutive patients with previously untreated multiple myeloma were studied for bone marrow plasma cell labeling index, response to peptichemio induction therapy, and rate of M-component (MC) changes during the course of the disease. They received intermittent melphalan or cyclophosphamide as maintenance therapy and peptichemio associated with vincristine at first relapse. The response rate (76%) was independent of clinical stage, evaluated according to Merlini et al and to Durie and Salmon. Among responsive patients, rapid responders (half-life of MC decrease less than 47 days for IgA and IgG and less than 29 days for light chain myelomas) had a bone marrow plasma cell labeling index significantly higher (P less than 0.01) than that of slow responders. Rapid responders had a median survival of 15 months, while slow responders had a median survival of 42 months (P less than 0.05). The difference in survival between the two groups was accounted for mainly by the difference in duration of first response and the different rates of MC increase following it. Both of these parameters were directly related to the half-life of MC decrease at response in IgA and IgG myelomas. The duration of second response and the half-life of MC increase following it were shorter than the duration of first response and than the half-life of MC increase at first relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

[Severe intoxication after combined chemotherapy of a sigma-adenocarcinoma with peptichemio and 5-fluorouracil (author's transl)].

After perioperative adjuvant chemotherapy of a sigma-adenocarcinoma with 400 mg peptichemio and 500 mg 5-fluorouracil a 61-year-old woman developed a severe intoxication: myelosuppression with pancytopenia, gastroenteritis and ulcerative proctitis, toxic hepato- and myocardiopathy, impaired renal function and alopecia. As a result of reduced resistance pneumonias, urinary tract infection, sepsis, cytomegaly infection and candidiasis of the oral mucosa occurred. The toxic effects are attributed mainly to the high dose of peptichemio.

Adenocarcinoma↗
PubMed1982

Combination chemotherapy with continuous infusion vinblastine and peptichemio for patients with advanced metastatic breast cancer.

Forty patients with metastatic breast cancer were treated with a combination of continuous 5-day infusion vinblastine and peptichemio. All patients had received prior therapy with 5-fluorouracil, adriamycin, cyclophosphamide and methotrexate. Vinblastine was given at a dose of 1.2 mg/m2/day for 5 days. Following completion of the 5-day infusion vinblastine, peptichemio was given as a rapid I.V. injection at a dose of 60 mg/m2. Ten partial responses (30%) were observed among the 33 evaluable patients with a median time to treatment failure of 6 months. Myelosuppression, predominantly granulocytopenia, was the major toxicity resulting from this combination. The response rate of this combination is not better than that observed with continuous 5-day infusion vinblastine alone.

Adult↗
PubMed1976

Peptichemio in children with neoplastic disease.

32 children with different types of tumors have bben treated with peptichemio. The efficacy was excellent in rhabdomyosarcoma and embrional sarcoma; encouraging in neuroblastoma, Wilms tumor and histiocytosis X. Side and toxic effects were minimal. In conclusion we can say that peptichemio is effective in oncologic diseases, but a larger number of patients is required in order to have a better knowledge about the antitumor activity of this drug.

Child↗