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PubMed1975

Antitumor activity of tetraacetylglucosamine mustard.

1,3,4,6-Tetra-O-acetyl-2-(di-2-chloroethyl)amino-2-deoxy-D-glucopyranose is active against L1210 leukemia, giving over 100% increased life-span at optimal dose. Against P388 leukemia, it gives 200% increased life-span with long-term survivors. The compound is most active when given i.p., but shows some activity when given s.c. than p.o., and is more potent (therapeutic and toxic effect) than mechlorethamine on both a molar and a mg basis. Of importance, the schedule dependency for the administration of 1,3,4,6-tetra-O-acetyl-2-(di-2-chloroethyl)amino-2-deoxy-D-glucopyranose in L1210 leukemia differs from most alkylating agents in that it is best given by multiple daily injections rather than as a single large injection on Day 1. This characteristic can be attributed to the amino-glucose moiety.

Acetylglucosamine↗
PubMed2002

Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer.

Curcumin, the major component of the spice turmeric, is used as a coloring and flavoring additive in many foods and has attracted interest because of its anti-inflammatory and chemopreventive activities. However, this agent also inhibits the generation of reactive oxygen species (ROS) and the c-Jun NH(2)-terminal kinase (JNK) pathway, and because many chemotherapeutic drugs generate ROS and activate JNK in the course of inducing apoptosis, we considered the possibility that curcumin might antagonize their antitumor efficacy. Studies in tissue culture revealed that curcumin inhibited camptothecin-, mechlorethamine-, and doxorubicin-induced apoptosis of MCF-7, MDA-MB-231, and BT-474 human breast cancer cells by up to 70%. Inhibition of programmed cell death was time and concentration dependent, but occurred after relatively brief 3-h exposures, or at curcumin concentrations of 1 microM that have been documented in Phase I chemoprevention trials. Under these conditions, curcumin exhibited antioxidant properties and inhibited both JNK activation and mitochondrial release of cytochrome c in a concentration-dependent manner. Using an in vivo model of human breast cancer, dietary supplementation with curcumin was found to significantly inhibit cyclophosphamide-induced tumor regression. Such dietary supplementation was accompanied by a decrease in the activation of apoptosis by cyclophosphamide, as well as decreased JNK activation. These findings support the hypothesis that dietary curcumin can inhibit chemotherapy-induced apoptosis through inhibition of ROS generation and blockade of JNK function, and suggest that additional studies are needed to determine whether breast cancer patients undergoing chemotherapy should avoid curcumin supplementation, and possibly even limit their exposure to curcumin-containing foods.

Animals↗
PubMed2003

Bilateral renal artery stenosis after abdominal radiotherapy for Hodgkin's disease.

A 49-year-old woman was admitted with fatigue, dyspnoea, pretibial oedema and decreased daily urination. Seven years ago she was treated with doxorubicin, bleomycin, vinblastine and dacarbazine, alternating with mechlorethamine, vincristine, procarbazine and prednisone and 80 Gy abdominal radiotherapy for Hodgkin's disease. Two years later, malignant hypertension was diagnosed. Angiotensin-2 antagonist and beta-blocker treatment was given. After increased serum creatinine levels were determined, renal angiography was performed and total obstruction in the left renal artery and near total obstruction in the right side was observed. She was admitted to our clinic with oliguria, and acute renal failure was diagnosed. Balloon angioplasty and stent implantation was performed to the right renal artery. After a polyuric period, serum creatinine reduced to near normal levels. Angiotensin-2 antagonist treatment worsened the course in this patient. Patients with resistant hypertension occurring years after abdominal radiotherapy should be evaluated for renal artery stenosis.

Abdominal Neoplasms↗
PubMed2003

Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas.

Cutaneous T-cell lymphomas (CTCLs) are a relatively uncommon group of lymphoproliferative disorders in which a malignant population of T cells is localized to the skin at presentation. Of the 4 classic CTCL phases (patches, infiltrated plaques, tumors, Sézary syndrome), the majority of patients present with early stage patch or plaque disease, which can usually be effectively managed using skin-directed therapies. Traditional skin-directed therapies include topical corticosteroids, topical chemotherapeutic agents (mechlorethamine, carmustine), electron beam therapy (local and total skin), and phototherapy (UV-A, UV-B). Each of these has demonstrated efficacy in early stage disease; however, with the exception of topical corticosteroids, all have some disadvantages and are associated with significant adverse events, particularly secondary skin malignancies and skin damage. Bexarotene is a synthetic retinoid analog that selectively activates retinoid X receptors. In clinical trials, bexarotene gel demonstrated efficacy for the topical treatment of cutaneous lesions in patients with stage IA or IB CTCL who have refractory or persistent disease following other therapies or who cannot tolerate other therapies. Initial evidence indicates that bexarotene gel may be active as first-line therapy in early stage disease. Its role in combination with other treatments remains to be determined. Topical bexarotene gel is generally well tolerated and offers patients greater convenience compared with traditional skin-directed therapies, with a flexible administration regimen. The availability of bexarotene gel provides patients and physicians with a new skin-directed treatment option for early stage CTCL.

Administration, Topical↗
PubMed2003

Management of mycosis fungoides: Part 2. Treatment.

Mycosis fungoides is a low-grade lymphoproliferative disorder of skin-homing CD4+ lymphocytes that may produce patches, plaques, tumors, erythroderma, and, ultimately, systemic dissemination. Treatment selection is generally guided by institutional experience, patient preference, and toxicity profile, as data from phase III clinical trials are limited. Effective topical treatments currently include mechlorethamine (Mustargen), carmustine (BCNU, BiCNU), corticosteroids, bexarotene (Targretin, a novel rexinoid), psoralen plus ultraviolet A, ultraviolet B, and total-skin electron-beam radiotherapy. Effective systemic treatments include interferon, retinoids, bexarotene, denileukin diftitox (Ontak), extracorporeal photopheresis, chemotherapy, and high-dose chemotherapy with allogeneic bone marrow transplant. Each of these treatments is discussed in detail, followed by specific recommendations for each stage of mycosis fungoides.

Administration, Topical↗
PubMedDate not supplied

Etoposide, vinblastine, adriamycin and prednisolone (EVAP) combination chemotherapy as first-line treatment for Hodgkin's disease.

BACKGROUND: Mechlorethamine, vincristine, procarbazine, prednisolone (MOPP) and doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) are well established first-line chemotherapy protocols for the treatment of Hodgkin's disease. The aim of this study was to try a new combination of drugs that individually have a proven efficacy in Hodgkin's disease but have less incidence of severe nausea, vomiting, pulmonary toxicity and sterility. METHODS: This prospective, single-arm study enrolled 66 newly diagnosed, previously untreated patients of Hodgkin's disease with stages IA (bulky)-IVB disease. They were given 6-8 courses of etoposide, vinblastine, doxorubicin and prednisolone (EVAP) as first-line chemotherapy between January 1992 and December 1997. Radiotherapy (RT) was given to the involved fields of those patients who had bulky (> or = 10 cm) stages I or II disease at presentation. The end-points were (i) complete and overall response; (ii) disease-free and overall survival; and (iii) toxicity. RESULTS: Complete response was seen in 78.8% and partial response in 12.2% of patients; the overall response rate was 91%. The median follow up was 48 months. The 5-year overall and disease-free survivals were 72% and 62%, respectively. There were 3 episodes of grade IV neutropenia requiring hospitalization. One patient developed avascular necrosis of the femur. There were 2 deaths during treatment, one due to chemotoxicity, and another due to progressive disease. CONCLUSION: The overall and complete responses were fractionally inferior to the recently published hybrid MOPP/ ABV combination and that of ABVD chemotherapy. The advantages of the EVAP combination are absence of pulmonary toxicity, markedly lower incidence of sterility and nausea and vomiting. EVAP is an attractive option and a randomized trial is warranted to assess its efficacy against established protocols.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Full clinical recovery after topical acyclovir treatment of Epstein-Barr virus associated cutaneous B-cell lymphoma in patient with mycosis fungoides.

Primary cutaneous T- and B-cell lymphomas are a heterogeneous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria has improved their recognition. Cutaneous B-cell and T-cell lymphomas are seldom found together in the same patient. Here we report a rare case of mycosis fungoides variant of a cutaneous T-cell lymphoma (CTCL) which later developed Epstein-Barr virus (EBV) associated cutaneous B-cell lymphoproliferative disorder. The patient initially presented with generalized erythroderma, extensive plaques, and axillary lymphadenopathy. Histopathology and immunophenotyping of her tumor from the right breast nodule revealed a T-cell lymphoma consistent with mycosis fungoides. She was initially treated with pentostatin, followed by topical mechlorethamine and topical steroids. After progression of her mycosis fungoides with worsening diffuse skin lesions on this regimen, her treatments were changed to oral bexarotene with an initial partial response followed by stable disease. Three years from her initial presentation, she developed ulcerated cauliflower-like nodules on her forehead. Biopsy of these lesions revealed EBV-positive large- and medium-sized pleomorphic B-cells consistent with EBV-driven B-cell lymphoproliferative disorder. She was treated with topical acyclovir cream on the involved skin areas while continuing with oral bexarotene for mycosis fungoides. Skin lesions gradually diminished and totally disappeared after four weeks of topical acyclovir treatment. Bexarotene treatment was continued for another year until the mycosis fungoides progressed and became wide spread causing her death four and a half years after the initial diagnosis. The coexistence of two cutaneous non-Hodgkin lymphomas of different lineage in the same patient and the complete clinical response of EBV-related B-cell cutaneous component to topical acyclovir makes this rare case particularly interesting.

Acyclovir↗
PubMed2005

Chemotherapy dosing in the setting of liver dysfunction.

Advanced cancer in the setting of liver dysfunction poses a dilemma for physicians, as many cancer chemotherapeutic agents undergo hepatic metabolism. Most cytotoxic drugs have a narrow therapeutic index, and the administration of chemotherapy to patients with liver impairment results in complicated safety issues. We present a concise review of cancer chemotherapy dosing in the setting of liver dysfunction. Although caution in treating all patients with hepatic failure is essential, the use of certain agents provokes greater concern than others. Continuous-infusion fluorouracil, capecitabine (Xeloda), mechlorethamine (Mustargen), cyclophosphamide, topotecan (Hycamtin), and oxaliplatin (Eloxatin) appear to be relatively well tolerated. On the contrary, taxanes, vinca alkaloids, irinotecan (Camptosar), and anthracyclines may cause unacceptable toxicity if administered to patients with poor hepatic function. For many anticancer agents, the paucity of data prohibits formal dosing recommendations, and most guidelines remain empiric.

Anthracyclines↗
PubMed1991

Interaction of N,N',N''-triethylenethiophosphoramide and N,N',N''-triethylenephosphoramide with cellular DNA.

The antineoplastic agents N,N',N''-triethylenethiophosphoramide (thioTEPA) and N,N',N''-triethylenephosphoramide (TEPA) were studied for their interaction with the DNA of L1210 cells in the presence and absence of rat hepatic microsomes and NADPH. Alkaline elution was used to study 3 types of DNA lesions. When L1210 cells were incubated with thioTEPA alone, or with thioTEPA in the presence of microsomes and NADPH, no single-strand breaks were detected. However, incubation of L1210 cells for 2 h with thioTEPA, at concentrations greater than or equal to 100 microM, caused a dose-dependent increase in interstrand cross-linking that reached a maximum by 2 h after drug exposure. In the presence of rat hepatic microsomes and NADPH, this cross-linking was eliminated, but a different DNA lesion, alkali-labile sites, was produced. These alkali-labile sites were partially reparable with maximum repair achieved by 2 h after removal of drug. ThioTEPA was greater than 85% consumed by the microsomal incubation conditions employed, and TEPA was the only product of the microsomal metabolism of thioTEPA. Alkaline elution studies of L1210 cells that had been incubated with TEPA, alone or in the presence of microsomes and NADPH, demonstrated an elution pattern identical to that produced by thioTEPA in the presence of microsomes and NADPH. Lymphoblastoid cell lines derived from patients with Fanconi's anemia were far more sensitive to thioTEPA and mechlorethamine hydrochloride than were lymphoblasts derived from normal humans, but this hypersensitivity was not noted with TEPA or bleomycin. This is consistent with the known hypersensitivity of cells from patients with Fanconi's anemia to agents that produce interstrand cross-links and with the alkaline elution studies described above. In contrast, lymphoblastoid cell lines derived from patients with ataxia telangiectasia were no more sensitive to thioTEPA than were lymphoblasts derived from normal humans but were far more sensitive to bleomycin. One of these cell lines proved hypersensitive to TEPA, whereas the other was no more sensitive to TEPA than were lymphoblasts from normal humans. Our data imply that thioTEPA produces interstrand cross-links but that TEPA, the primary metabolite of thioTEPA, produces DNA lesions that are alkali labile.

Animals↗
PubMed1991

[Local treatments of cutaneous psoriasis].

Most of psoriatic patients require topical therapy. Dermal application of drugs may be the unique treatment; but it can also combined with oral drugs, or phototherapy. Patients are treated at home or in day-care centers; some require hospitalization. Topical corticosteroids are widely used: abuses are frequently observed, therefore skin and systemic side-effects may occur to varying degrees. Tars are still useful. Short-contact anthralin is active and well tolerated, and compliance is better than with conventional tar therapy, especially in children. Topical mechlorethamine clears the plaques but contact dermatitis may occur. New therapeutic approaches include Vitamin D3 analogues.

Administration, Topical↗
PubMed1991

[Psoriasis. Therapeutic strategy].

The strategy of psoriasis treatment consists first in informing the patients about the too quick renewal of their skin with, as a consequence, the necessity of two phases in the treatment; the clearing phase aimed at suppressing the skin lesions, and a maintenance phase where it is necessary to continue the treatment on an apparently normal skin in order to avoid relapse. For local treatments (tar, anthralin, topical local steroids, mechlorethamine, vitamin D3 derivatives and ointment) and for systemic treatment (UVB, PUVA therapy, retinoids, cyclosporine or methotrexate) it is necessary that the inconvenience of the treatments (due to modifications in everyday life and due to side effects) be less important than the decrease of life quality due to psoriasis. The aim is not to clear psoriasis but to increase the quality of life of the patients. A peculiar strategy of treatment is necessary for some forms of psoriasis like flexural psoriasis, psoriasis arthritis, ungueal psoriasis, palmoplantar psoriasis, pustular psoriasis, psoriatic erythroderma and psoriasis of the child. With the various treatments that we have now, used alone or in association, it is possible to improve the quality of life of nearly all psoriatic patients.

Administration, Cutaneous↗
PubMed1991

Nine years' experience with ABMT in 128 patients with Hodgkin's disease: an Italian study group report.

One-hundred, twenty-eight patients with Hodgkin's disease in remission or who had failed a mechlorethamine, vincristine, procarbazine and prednisone (MOPP), a doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and/or lomustine, etoposide and prednimustine (CEP) regimens have been treated with a high-dose therapy (HDT) containing cyclophosphamide, etoposide, carmustine (CVB) and autologous bone marrow transplantation (ABMT). Forty patients were treated while they were in resistant or progressive disease states using alternating MOPP/ABVD protocol; 15 patients received ABMT in first relapse; 51 patients had a complete remission (CR) with first-line therapy but later relapsed and then received conventional salvage therapy; 16 achieved no response or progression ("resistant relapse" patients) and 35 responded partially or completely ("sensitive-relapse" patients). The other 22 patients received ABMT in remission. Following HDT, 56 patients (52.8%) achieved CR and 23 patients (21.6%) achieved a partial remission for an overall response rate of 74.4%. Sixteen patients failed to respond and died in progressive disease 1 to 10 months (median 6 months) after ABMT. High-dose therapy produced severe toxicity including vomiting (100%), mucositis (75%) and liver enzymes and alkaline phosphatase elevations (51%). There were 10 treatment-related deaths. A multivariate analysis identified poor performance status and resistant-relapse patients as very important adverse risk factors for survival immediately after ABMT. These results, while validating this procedure for inducing remissions in advanced highly-treated patients, at the same time confirm the need of employing this approach in first relapse or in second complete remission after standard therapy and before ABMT or, in first complete remission in very high risk Hodgkin's disease patients. Our experience in 15 very poor prognosis Hodgkin's disease patients transplanted in first CR demonstrated to be much significant.

Adult↗
PubMed1991

[Psoriasis: development and fatal complications].

In a retrospective study we tried to evaluate the number of severe psoriasis with a lethal outcome observed in France in a 20-year period from 1965 to 1985. Among 992 psoriatic in-patients on care during this period in the Dermatology Clinic of Strasbourg, 7 died of different complications directly related to the skin disease or its therapy; 39 further cases could be gathered through different departments of dermatology of France. Patients who died had generalized psoriasis (13 cases), psoriatic erythroderma (15 cases) and generalized pustular psoriasis (18 cases); 18 (39 p. 100) also had psoriatic polyarthritis. Circumstances leading to death (table I) were metabolic disorders, related to erythroderma in most cases, non-specific complications (infections, amyloidosis) or complications of specific treatments (methotrexate, etretinate, corticosteroids, mechlorethamine). A comprehensive review of the literature over a century showed that only 72 lethal psoriasis cases have been reported: this rather low number may be due to the fact that some rare pathologies, such as visceral amyloidosis (12 cases) (table III) and fatal complications of methotrexate therapy (38 cases) (table V), paradoxically are more often published than non-specific complications occurring in severe psoriasis, such as cardiovascular failure or cachexy in erythrodermic patients. However, the review of the literature shows, as our own inquiry, the poor prognosis of generalized pustular forms and of psoriasis-associated polyarthropathies: among 42 lethal cases where enough data were available, 23 (55 p. 100) had psoriatic polyarthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Treatment of Hodgkin's disease.

The available data support the hypothesis proposed by Smithers that Hodgkin's disease appears to be a systemic disorder of the lymphatic system. Standard treatments have been developed that cure approximately 70% of all patients who present to most institutions. Physicians should know the treatment approaches before proceeding with staging, because intelligent use of the best available treatment often obviates the need for staging laparotomy. At present, it is best that either chemotherapy or radiotherapy be used alone, except in patients who have massive mediastinal disease and for whom combinations of radiotherapy and combination chemotherapy are superior. Despite the long series of clinical trials conducted over the past two decades, no combination of four drugs has improved the results obtained with the original mechlorethamine-vincristine-procarbazine-prednisone program, when it is given in sufficient doses. It has been assumed that drug resistance of a specific type was the major reason for treatment failure. Attempts by physicians to overcome drug resistance, using alternating cyclical non-cross-resistant combination chemotherapy, have thus far not proved this approach to be superior to the use of a four-drug combination in full doses, and call into question this approach to testing the Goldie-Coldman hypothesis. Dose intensity has been a poorly controlled variable in virtually all clinical trials in Hodgkin's disease, and inadequate dosing may be the prime reason for treatment failure. This point has been highlighted by recent excellent results with marrow-ablative, high-dose chemotherapy and autologous bone marrow transplantation support for patients with very advanced "drug-resistant" disease. Investigators are now attempting to improve dose intensity by using more concentrated versions of standard drug combinations with colony-stimulating factors for support.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Induction of fos RNA by DNA-damaging agents.

We have found that a wide variety of DNA-damaging agents and heat shock increase fos RNA to different extents in Chinese hamster ovary cells. These include the monofunctional alkylating agents methylmethane sulfonate and N-methyl-N'-nitro-N-nitrosoguanidine, the cross-linking agents cis-Pt(II) diamminedichloride and mechlorethamine HCl, the DNA base-damaging agents 4-nitroquinoline-N-oxide and N-acetoxy-2-acetylaminofluorene, ultraviolet and near-ultraviolet radiation, hydrogen peroxide, and Adriamycin. Prolonged increases in fos RNA were observed, with persistence to 16 h following treatment. Variation in the amount of fos RNA induction by these agents and the diverse types and frequencies of cellular damage produced by them suggested that there might be several different mechanisms responsible for increased fos RNA.

Animals↗
PubMed1989

European experience with ifosfamide in lymphomas.

In malignant lymphomas, ifosfamide-containing regimens were at first used mainly in second-line therapy and response-adapted protocols. Currently, in combination with other drugs, ifosfamide is being used in several phase-III trials. As salvage therapy in non-Hodgkin's lymphoma (NHL), IMV-Bleo (ifosfamide, methotrexate, etoposide, bleomycin) produced a complete remission (CR) rate of 41% and seemed to be particularly effective in patients with suboptimal response to first-line treatment. IBEP (ifosfamide, bleomycin, etoposide, procarbazine), in combination with procarbazine and bleomycin was an effective non-cross-resistant alternative in CHOP (cyclophosphamide, hydroxydauomycin/doxorubicin, vincristine, prednisone)-refractory NHL. In a trial of response-oriented therapy in high-grade malignant lymphoma patients, the investigators concluded that consolidation therapy was necessary even in patients with rapid response to CHOP. Patients with NHL resistant to or relapsing from conventional chemotherapy or with MOPP-ABVD (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, decarbazine)-resistant Hodgkin's disease (HD) were treated with BMV-VIP [bleomycin, plus high-dose methylprednisolone plus ifosfamide, etoposide, plus methylprednisolone]. In high-grade malignant NHL, patients received three cycles of COP-BLAM (cyclophosphamide, vincristine, procarbazine, prednisone, bleomycin, doxorubicin). Those who achieved CR received two more cycles of COP-BLAM and IMV (ifosfamide, methotrexate, etoposide) as consolidation therapy. Patients in partial remission (PR) or with less of a response to COP-BLAM were switched to IMV. After reaching CR, patients received two additional cycles as consolidation therapy. After the second restaging, patients were randomized to observation v additional radiotherapy. Of 191 patients, 148 have passed first restaging with 51% in CR; 85 went through the second restaging with 61% in CR. Of 32 patients who only reached PR after the first restaging, 15 (47%) achieved CR with IMV. For primary treatment of HD, the German Hodgkin Study Group added a third non-cross-resistant regimen, IMEP (ifosfamide, methotrexate, etoposide, prednisone), to supplement COPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABV in the primary treatment of HD. In a pilot study, 87% of 63 evaluable patients reached CR. The current phase-III protocol is comparing COPP/ABVD with fast alternating cycles of COPP/ABV/IMEP.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Results of recent salvage chemotherapy regimens for lymphoma and Hodgkin's disease.

From 1981 to 1983, 208 patients with recurrent or refractory lymphoma were treated with methylglyoxal-bis-guanylhydrazone (methyl-GAG), ifosfamide, methotrexate, etoposide (MIME). The complete remission (CR) rate was 24% and CR plus partial remission (PR) was 60%. Response was higher for aggressive than for indolent cell types. Median duration of CRs was 16.5 months and median survival of all patients was 9 months. In view of the in vitro synergism between cisplatin and high-dose cytarabine, we recently designed the DHAP regimen, which consists of cisplatin, 100 mg/m2 IV over 24 hours; cytarabine, 2 g/m2 IV over two hours every 12 hours for two doses; and dexamethasone, 40 mg orally daily for 4 days. There were 28 of 90 (31%) CRs and 22 of 90 (24%) PRs. Median duration of CR is 15 months; median survival of all patients is 6 months. The major toxicities have been infection (31%) and moderate to severe renal dysfunction (20%). In contrast to MIME, response rates did not differ significantly between aggressive and indolent cell types. A high-dose regimen (CBV) consisting of cyclophosphamide, 6 g/m2; carmustine, 300 mg/m2; and etoposide, 250 mg/m2 daily for 3 days followed by autologous bone marrow transplant (ABMT) has been successfully used to treat 62 patients with Hodgkin's disease recurrent or refractory after mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, dacarbazine (MOPP/ABVD)-like regimens. A CR rate (47%) has been observed; 83% of these CRs remain alive and free of disease with a median follow-up of 19 months. This regimen appears to have curative potential in 40% of all cases and in 60% of cases treated after the first or second relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Phase II trial of ifosfamide in children with malignant solid tumors.

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.

Adolescent↗