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PubMed2005

Long-term results of autologous stem cell transplantation for Hodgkin's disease (HD) and low-/intermediate-grade B non-Hodgkin's lymphoma (NHL): a report from the Austrian Stem Cell Transplantation Registry (ASCTR).

Between 1990 and 2001, 68 patients with advanced Hodgkin's disease (HD) and 86 patients classified as low-/intermediate-grade B non-Hodgkin's lymphoma (NHL) were reported to the Austrian Stem Cell Transplantation Registry (ASCTR). Following autologous stem cell transplantation (SCT) for HD, overall survival was 56% [95% confidence interval (CI): 40-72%] with a disease-/progression-free survival of 49%, reaching a plateau at 5 years. Using multivariate Cox regression analysis BEAM conditioning (carmustine, cytarabine, etoposide and melphalan) was predictive for favourable outcome, better disease-/progression-free survival and a significantly lower risk for relapse. The cumulative incidence of relapse was 30%, even for patients in complete remission at time of SCT. The cumulative risk for developing a secondary malignancy increased continuously over time, achieving 20% at 7 years and 46% at 10 years with previous radiotherapy as the only risk factor in the multivariate analysis. Overall survival for NHL patients was 45% (95% CI: 26-64%) with a disease-/progression-free survival of 26% at 7 years. In the multivariate Cox regression analysis stage of disease at time of SCT was the most powerful parameter for overall survival, disease-/progression-free survival and relapse. Mantle cell lymphoma, greater than or equal to three lines of previous therapy, and a conditioning regimen other than BEAM were also predictive for death. The main reason for treatment failure was relapse (cumulative incidence 54-75%). Because of the high risk of relapse/progression in both disease categories and the additional high rate of second malignancies in HD patients, allogeneic stem cells should be considered a valuable alternative for selected patients. The efficacy of allotransplantation following reduced-intensity conditioning should be tested in randomised trials.

Adolescent↗
PubMed2005

Autologous tandem transplantation in patients with primary progressive or relapsed/refractory lymphoma.

Patients with primary progressive or refractory Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL) have a particularly poor prognosis. Here we report the results of autologous tandem transplantation in these patients. Patients aged 18-55 years with primary progressive or refractory relapsed HD and aggressive NHL were included. Patients received high-dose etoposide (2000 mg/m(2)) followed by peripheral blood stem cell harvest (PBSC). The first high-dose chemotherapy (TMC) consisted of thiotepa (750 mg/m(2)), mitoxantrone (40 mg/m(2)), and carboplatin (990 mg/m(2)). Patients with no change (NC), partial remission (PR), or complete remission (CR) after TMC then received BEAM with carmustine (300 mg/m(2)), etoposide (1200 mg/m(2)), cytarabine (1600 mg/m(2)), and melphalan (140 mg/m(2)). Patients with bulky disease (>5 cm) or residual lymphoma received involved field radiotherapy. Twenty-five patients were included (HD=10, NHL=15, median age 34 years). Two patients with HD achieved a CR and five patients a PR [response rate (RR) 70%]. Three patients (30%) experienced treatment failure including two deaths due to peritransplant complications. Five patients with aggressive NHL were in CR and two patients in PR (RR 46%). Of the eight patients (56%) with treatment failure, three had progressive disease and five died from peritransplant complications. Freedom from treatment failure (FFTF) and overall survival (OS) for all patients after 12 months was 28% and 40%, respectively. Tandem HDCT followed by autologous stem cell transplantation (ASCT) offers a chance of cure in these poor prognostic patients, but is associated with risks.

Adult↗
PubMed2000

High-dose therapy with peripheral blood stem cell transplantation for patients with relapsed or refractory Hodgkin's disease: long-term outcome and prognostic factors.

From March 1986 to March 1998, 82 patients with relapsed or refractory Hodgkin's disease underwent high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) transplantation in our center. This is a retrospective analysis of the long-term clinical outcome. There were 52 males and 30 females with a median age of 32 years (range 18-59 years). Prior to transplantation, 36 patients were in complete remission (CR), 34 in partial remission (PR), and 12 had refractory disease after salvage therapy. For HDCT, 78 patients were treated with CBV (cyclophosphamide, 6.0-6.8 g/ m2; etoposide, 1.0-1.6 g/m2; carmustine, 0.45-0.8 g/m2), while four patients received different regimens. Probability of freedom from progression (FFP), overall survival (OS), and event-free survival (EFS) at 5 years of the entire group was 63%, 61%, and 54%, respectively. Early mortality rate ( < or = 100 days) declined from 17% to 6% after 1992. Five patients died of late transplant-related complications (> 100 days), including secondary lymphoma and leukemia in two patients. None of the refractory patients survived beyond 3.5 years. Multivariate analyses identified extranodal sites of disease at relapse and refractory disease status prior to transplantation as significant prognostic factors for FFP, EFS, and OS. As we have shown in our study, remarkable progress was achieved in reducing early morbidity and mortality over time, but this was associated with only a slight, not significant improvement of long-term outcome (OS 66% vs 57% at 5 years for patients undergoing PBSC transplantation before and after 1992, P = 0.26). Although the results as a whole are encouraging for chemosensitive patients, new therapeutic strategies are needed to reduce toxicity and improve the clinical outcome of patients, especially of those with a less favorable prognosis.

Adolescent↗
PubMed1997

Human tumor models in the severe combined immune deficient (scid) mouse.

PURPOSE: To test a number of established human tumor cell lines and early passage breast cancer (UACC2150) and melanoma cells (UACC1273) for growth in the scid mouse and the tumors' response to conventional chemotherapeutic drugs. METHODS: Established melanoma (A375, C81-61), colon (SW480), lung (A549), lymphomoblastoid leukemia (LCL-B), promyelocytic leukemia (HL60), prostate (PC-3, DU145), and breast (MCF7) cell lines were injected at subcutaneous (s.c.), intraperitoneal (i.p.), or mammary fat pad (MFP) sites. Tumor volume growth curves and survival curves were established for the various tumor cell lines. Carmustine (BCNU), cisplatin (CDDP), cyclophosphamide (CPA), doxorubicin, dacarbazine (DTIC), tamoxifen and vincristine were injected s.c. or i.p.. The chemotherapeutic drug effects on tumor volumes and survival were determined. RESULTS: Tumor growth occurred with each cell type. After i.p. injection, 90% mortality occurred within 26 to 60 days except for the early passage melanoma cell line UACC1273 with which mortality occurred within approximately 90 days. In the MCF7 breast model, treatment with tamoxifen (P < 0.001) and CPA (P < 0.0001) resulted in significant tumor growth delay compared with control groups. BCNU and CDDP resulted in significant tumor growth delays relative to control in SW480 colon cancer (P < 0.0014) and A375 melanoma (P < 0.0001) models, respectively. CPA and doxorubicin improved survival in the HL60 leukemia model (P = 0.0018). CONCLUSIONS: These scid mouse human tumor models appear to reflect the clinical situation in that clinically active chemotherapeutic drugs are similarly active in the scid mouse models. Therefore, the scid mouse models may be useful for testing new chemotherapeutic agents against various human cancer types.

Animals↗
PubMed1999

Failure of taxol-based combination chemotherapy for malignant glioma cannot be overcome by G2/M checkpoint abrogators or altering the p53 status.

In an effort to develop more effective forms of adjuvant chemotherapy for malignant brain tumors, we sought to develop a taxol-based combination chemotherapy regimen for glioma cell lines in vitro. Here, we report that coexposure of LN-229 or T98G glioma cells to taxol and either doxorubicin, camptothecin, cytarabine, or VM26 resulted in antagonistic effects rather than additive or synergistic cytotoxicity. There were no interactions of taxol with the effects of carmustine (BCNU) or vincristine. Antagonism was more prominent in cytotoxic cell death assays than in clonogenic cell death assays and was not overcome by G2/M checkpoint abrogators such as caffeine or pentoxyfilline. Ectopic expression of mutant and wild-type p53val135 attenuated taxol cytotoxicity in both T98G cells, which are mutant for p53, and LN-229 cells, which exhibit functional wild-type p53 activity. Interestingly, wild-type p53val135 abrogated the taxol-imposed G2/M arrest in both cell lines. However, wild-type p53val135 did not promote glioma cell killing by combinations of taxol and any of the other drugs. Further, an analysis of a panel of 12 human glioma cell lines revealed no relationship between genetic or functional p53 status and taxol sensitivity. In summary, combination either with other chemotherapy drugs, with abrogators of the G2/M checkpoint, with wild-type p53 gene transfer was not a promising approach for a taxol-based combination chemotherapy regimen in malignant glioma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Chemosensitivity of glioma cells in vitro: a meta analysis.

PURPOSE: The disappointing results of chemotherapy in glioblastoma might be caused by the choices of agents, which mostly include nitrosurea. We compared the in vitro efficacy of chemotherapeutic agents, developing a method to summarize published data. METHOD: Between 1966 and 1995 chemotherapy in glioma cells was reported in 1643 articles. Efficacy was mostly described by the drug concentration that killed 50% of the cells (LC50). It was measured with various cell-culture techniques, of which a colorimetric test [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltrazolium bromide] was mostly used. We calculated factors from these data to transform results to LC50 values as if the colorimetric test was used in all of them. This allowed data from all publications to be summarized in a new type of meta analysis. RESULTS: The most important agents and the average LC50 values (mg/l) were actinomycin-D 0.042, vincristine 0.075, mitoxantrone 0.12, vinblastine 0.21, doxorubicin 0.29, diaziquone 0.76, cisplatin 1.1, methotrexate 1.1, cytasine arabinoside 1.59, 5-flurouracil 2.33, bleomycin 18.6, carboplatin 29.8, carmustine 37.0, nimustine 48.9, and lomustine 76.7. The most resistant cell was SNB56, followed with increasing sensitivity by SF128 and A172, and primary cultures P497, SF210, U87MG, SF126, 9L, P540, U251MG, HU62, C6. The complete list of original data is available upon request. CONCLUSION: The efficacy of nitrosourea in vitro is low.

Antineoplastic Agents↗
PubMed2002

Recurrent malignant glioma in adults.

Meaningful palliation is possible for selected patients with recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) using aggressive treatment. Although long-term disease-free survival occurs in fewer than 10% of patients, most who achieve such survival have been treated for multiple recurrences. Surgical resection with the placement of lomustine-releasing wafers is the only therapy proven in randomized trials to be beneficial for recurrent malignant gliomas. Reoperation is indicated when local mass effect limits the quality of life. Reoperation may make other treatments more effective by removing treatment-resistant hypoxic cells and thereby prolonging high-quality survival. Combination chemotherapy (including procarbazine and a nitrosourea) provides dramatic benefit for many recurrent anaplastic or aggressively behaving oligodendrogliomas and anaplastic mixed oligoastrocytomas. For other recurrent malignant gliomas, single-agent cytotoxic chemotherapy (eg, intravenous lomustine or platinums, oral carmustine, temozolomide, or procarbazine) appears to provide equivalent results and better quality of life at a lower cost than do the combinations of cytotoxic drugs. A randomized phase II trial demonstrates that temozolomide provides longer progression-free survival and better quality of life than standard-dose procarbazine in patients with recurrent glioblastoma multiforme. Because benefits of available cytotoxic chemotherapy for anaplastic astrocytoma and glioblastoma are small, participation in clinical trials is appropriate for most patients. Reirradiation (using stereotactic or three-dimensional conformal techniques with or without concomitant cytotoxic chemotherapy) as radiation sensitization can prolong high-quality survival in selected patients. Specific examples include radiosurgery with the gamma knife or with linear accelerators, intracavitary radiation with the newly US Food and Drug Administration-approved GliaSite (Proxima Therapeutics, Alpharetta, GA) radiation therapy system, low dose rate permanent-seed brachytherapy, and high dose rate stereotactic brachytherapy. Dexamethasone (used for the shortest time in the lowest effective doses) can provide symptomatic benefits. Osmotic diuretics such as mannitol reduce cytotoxic edema more rapidly.

Adult↗
PubMed2005

Intra-arterial chemotherapy of primary brain tumors.

Intra-arterial (IA) chemotherapy is a form of regional delivery to brain tumors, designed to enhance the intra-tumoral concentrations of a given drug, in comparison with the intravenous route. Drugs that are likely to benefit from IA delivery have a rapid systemic clearance and include carmustine and other nitrosoureas, cisplatin, carboplatin, etoposide, and methotrexate. Clinical studies have demonstrated activity of IA chemotherapy approaches for low- and high-grade gliomas, and for cerebral lymphomas. However, a survival benefit for IA drug delivery, in comparison with intravenous administration, has not been proven in phase III trials. The technique is limited by the potential for significant vascular and neurologic toxicity, including visual loss, stroke, and leukoencephalopathy. More recent studies suggest that toxicity can be reduced by the use of carboplatin- and methotrexate-based regimens. Further clinical studies will be needed to determine the appropriate role for IA chemotherapy in the treatment of primary brain tumors.

Antineoplastic Agents↗
PubMed2006

Current therapeutic approaches in patients with brain metastases.

The development of brain metastases is often viewed as the end stage of a disease course and engenders skepticism about the efficacy of treatment. Aggressive management of brain metastases is effective in both symptom palliation and the prolongation of life. The majority of patients with controlled intracranial metastases will expire from systemic disease rather than from recurrence of these metastases. Single brain metastases should be treated with surgical resection or stereotactic radiosurgery, though it is unclear at this time if one modality is more effective than the other. Surgical resection is preferred when a pathologic diagnosis is needed, for tumors larger than 3.5 cm, or when immediate tumor mass decompression is required. Stereotactic radiosurgery (SRS) should be applied for single tumors less than 3.5 cm in surgically inaccessible areas and for patients who are not surgical candidates. Small tumors (ie, < 3.5 cm) that cause minimal edema and are surgically accessible may be treated with either surgery or SRS. There is controversy over whether whole brain radiation therapy (WBRT) can be omitted following surgical resection or SRS. Omission of WBRT increases intracranial tumor recurrence; however, this has not been correlated with decreased survival. Clinicians who choose to omit upfront WBRT are obligated to monitor the patient closely for intracranial recurrence, at which time further salvage therapy in the form of surgery, SRS, or WBRT may be considered. Histology is of particular importance when considering WBRT for patients with radioresistant tumors such as melanoma, renal cell carcinoma, or sarcoma. WBRT may be of less clinical benefit in this setting. Chemotherapy has been demonstrated to improve response rates when used as an adjunct to radiation therapy. These improvements in response rates have not been correlated with an improvement in median survival. Noncytotoxic radiosensitizing agents such as motexafin and efaproxiral show promise. Phase III trials to assess the benefit of motexafin in patients with metastatic lung cancer and efaproxiral in patients with metastatic breast cancer are ongoing. Targeted therapies offer promise in achieving therapeutic efficacy while minimizing side effects. Surgical adjuncts such as BCNU (carmustine) wafers and the GliaSite Radiation System (Cytyc Corporation, Marlborough, MA) may be useful in the future in achieving optimal local tumor control.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1980

Cytotoxic drug-induced pulmonary disease: update 1980.

Administration of a number of cytotoxic agents has been associated with interstitial pneumonitis, alveolitis and pulmonary fibrosis. Some (bleomycin, busulfan, methotrexate) are well known to cause this problem, and others (carmustine, semustine, zinostatin, mitomycin, and chlorambucil) have only recently been recognized to do so. We review and update the available information about this form of drug toxicity. Interaction between these drugs and thoracic radiation or high oxygen fractions in inspired air has produced pneumonitis at doses lower than when the drug is used alone. Synergism between the drugs themselves when given concurrently also produces pulmonary toxicity at lower doses. With some drugs and in some patients steroids will diminish the pulmonary abnormalities, but death from hypoxia is a frequent outcome. Since early recognition of the problem and withdrawal of the injurious agent is the best treatment, physician awareness of and alertness to this toxicity and its relative risk is most important. The discovery of analogs of bleomycin with a better therapeutic index, specifically reducing pulmonary damage, is one of the goals of current cancer drug development.

Alkylating Agents↗
PubMed1991

Autologous bone marrow transplantation for patients with relapsed Hodgkin's disease.

PURPOSE: High-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkin's disease. Because patients with relapsed Hodgkin's disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkin's disease. PATIENTS AND METHODS: We treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT. RESULTS: The results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04). CONCLUSION: ABMT is a more effective therapy when used early for patients with relapsed Hodgkin's disease.

Adolescent↗
PubMed1992

Hepatocyte toxicity of mechlorethamine and other alkylating anticancer drugs. Role of lipid peroxidation.

The alkylating anticancer drugs, mechlorethamine (HN2), chlorambucil, cyclophosphamide, carmustine and lomustine readily induced cytotoxicity in isolated rat hepatocytes. Hepatocyte glutathione (GSH) was depleted rapidly following addition of the drugs. Lipid peroxidation ensued following GSH depletion and before cytotoxicity occurred. Furthermore, cytotoxicity was delayed by the antioxidants butylated hydroxyanisole (BHA) and alpha-tocopherol, the ferric iron chelator desferoxamine or the radical trap 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) even when added 10 min later. HN2 was much less toxic to hepatocytes under nitrogen and caused much less lipid peroxidation than under aerobic conditions. Cytotoxicity induced by HN2 was also prevented by choline, suggesting that a choline carrier is responsible for HN2 uptake in the hepatocytes. Various sulfur compounds acted as antidotes for HN2 cytotoxicity. Thiosulfate was still effective when added 30 min after HN2. Depletion of GSH in the hepatocytes markedly increased their susceptibility to HN2. However, BHA, desferoxamine or TEMPO protected these hepatocytes from HN2. This suggests that antioxidants could prove useful in preventing the increased risk of hepatotoxicity if GSH-depleting agents are used to overcome tumor resistance to nitrogen mustards.

Alkylating Agents↗
PubMed1995

Inhibition of glutathione-related enzymes and cytotoxicity of ethacrynic acid and cyclosporine.

Glutathione (GSH) is an endogenous thiol that detoxifies active oxygen and reactive species formed during intermediary metabolism and drug detoxification. Compounds with a range of potential toxicities were tested for their abilities to affect GSH reductase and GSH S-transferase activities, which are each components of the two principal detoxification pathways in which GSH participates. A high performance liquid chromatographic method for determining oxidized and reduced GSH was modified to assay GSH reductase activity. With this method it was possible to demonstrate that ethacrynic acid, which inhibits GSH S-transferase, also inhibits the activity of GSH reductase. Inhibition of GSH reductase by ethacrynic acid was similar to that seen with carmustine (BCNU). GSH reductase activity was not affected by cis- or transplatin, buthionine sulfoximine, other loop diuretics, cyclosporine A or aminoglycosides. Cyclosporine inhibited GSH S-transferase at 50 microM and higher concentrations. These results support a role for GSH-mediated detoxification mechanisms in ethacrynic acid- and cyclosporine-associated cytotoxicity, which may mediate their toxicities and their potential as adjunctive agents in antineoplastic therapy. A better understanding of the mechanism of their toxicity can greatly extend the clinical usefulness of these agents, as this toxicity is the basis of both their therapeutic and antitherapeutic actions.

Animals↗
PubMed1989

The problem of the quiescent cancer cell.

1. Antimetabolites and inhibitors of DNA topoisomerase II are relatively ineffective against quiescent cells. 2. Alkylating agents (carmustine, cisplatin) retain significant activity against Q-cells. 3. Of the various cytokinetic reasons why tumors may have slow growth rates (long cycle times, high cell loss factors, differentiation, Q-cells), modeling studies suggest that the presence of a large Q-cell compartment has the most serious implications for chemotherapy. 4. Agents may be active against Q-cells for two reasons: (a) Direct cytotoxicity that is not dependent upon cell proliferation, e.g., direct DNA damage or ATP depletion. (b) Drug accumulation and retention within the cells, resulting in delayed cytotoxicity when the cell re-enters the cell cycle. 5. Q-cells have low rates of RNA synthesis, very low rates of DNA synthesis, and relatively normal ribonucleotide pools. Though earlier results suggest that RNA synthesis is an exploitable target for Q-cell cytotoxic agents, the RNA synthesis inhibitor NSC 366140 did not inhibit RNA synthesis in Q-cells. 6. The pyrazoloacridine, NSC 366140, retained a high level of activity against quiescent cells, as did other pyrazoloacridine compounds with a 9-methoxy substitution. 7. Successful chemotherapy of carcinomas with high Q-fractions will probably require the development of new Q-cell active drugs with sites of action other than DNA. The antimetabolite APP-MP is an example of a non-DNA-directed agent active against Q-cells.

Animals↗
PubMed1995

Sensitivity of camptothecin-resistant human leukemia cells and tumors to anticancer drugs with diverse mechanisms of action.

Human leukemia U-937 cell clones resistant to 9-nitrocamptothecin (9NC) appear after exposure to increase 9NC-concentrations. Drug resistance is irreversible, regardless of whether the 9NC-resistant (U-937/CR150) cells grow in media with or without 9NC. U-937/CR150 cells are more sensitive than wild type U-937 (U-937/wt) cells to topoisomerase II-directed drugs, amsacrine, daunorubicin, and etoposide. The mitotic inhibitor, vincristine, induces hyperdiploidy in U-937/wt, but not in U-937/CR150 cells, whereas the antimetabolites, cytarabine and methotrexate, and the nitrosourea, carmustine, elicit similar responses in both U-937/wt and U-937/CR150 cells. U-937/CR150-generated tumors in nude mice are sensitive to etoposide. The clinical implications of increased sensitivity of 9NC-resistant tumors to some anticancer drugs are discussed.

Animals↗
PubMed1990

Validation of clinical predictive value of in vitro colorimetric chemosensitivity assay in head and neck cancer.

For chemosensitivity testing, a rapid in vitro colorimetric method (MTT assay) was used. Eleven head and neck cancer cell lines were investigated to distinguish five known active agents from five compounds inactive in phase II studies. Evaluation of the reliability of the assay for assessing drug sensitivity in this tumor cell population was done by correlating the in vitro results with reported in vivo response data. Methotrexate and cisplatin (clinically active) and vindesine and doxorubicin (less active clinically) were recognized in vitro as active and correlated well with clinical experience. Bleomycin (clinically active) was ineffective against some cell lines. The in vitro findings for the clinically inactive drugs (deoxyazacytidine, lomustine, and carmustine) also corresponded. Amsacrine and etoposide, contrary to clinical experience, showed activity in vitro. Further comparison of MTT assay results with clinical data is warranted and essential before its use in large-scale drug screening studies.

Antineoplastic Agents↗
PubMed1990

Activity of cytostatic drugs in two heterotransplanted human testicular cancer cell lines with different sensitivity to standard agents.

Two established human testicular cancer cell lines were used in a mouse xenograft model to assess the antitumour activity of 15 anticancer agents. Line H 12.1 was highly sensitive to cisplatin, bleomycin and vinblastine, resembling non-pretreated testicular tumours, whereas line H 23.1 showed resistance to cisplatin and vinblastine, comparable to tumours with acquired or intrinsic drug resistance. In line H 12.1 several drugs were highly active, including cyclophosphamide, ifosfamide, nimustine and vincristine; carmustine, vindesine, doxorubicin, epidoxorubicin, pirarubicin, mitoxantrone, carboplatin and iproplatin had only moderate activity. In line H 23.1 only cyclophosphamide, ifosfamide, nimustine, vincristine and bleomycin had antitumour activity. These two cell lines represent a useful model for preclinical evaluation of new agents with presumed activity in testis cancer.

Animals↗
PubMed1990

Basement membrane collagen-degrading activity from a malignant tumor is inhibited by anthracycline antibiotics.

Type IV collagenase activity was previously identified and purified to 7500-fold in homogenates from murine Walker 256 carcinoma, using acetylated [3H]-type IV collagen as a substrate. Anthracycline antibiotics daunorubicin, doxorubicin and epirubicin exhibited a non-competitive, reversible inhibition with Ki 92, 49 and 40 microM, respectively. This inhibitory effect, at therapeutically attainable concentrations of the forementioned antineoplastic drugs, may contribute, at least in part, to their antimetastatic properties. The anthracycline derivatives: 4-demethoxydaunorubicin, 4'-iododoxorubicin and 4-demethoxy-3'-deamino-3'-hydroxyepirubicin were without inhibitory effects at comparable concentrations. Other antineoplastic agents, such as belomycin, carmustine, cisplatine, etoposide, methotrexate, mitotane and teniposide did not exhibit any inhibitory effect at concentrations up to 1.0 mM.

Animals↗