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High dose chemotherapy and peripheral blood stem cell transplantation for high risk primary breast cancer: a single center experience in Thailand.

Twenty patients with high risk primary breast cancer underwent a high dose chemotherapy program at Ramathibodi Hospital, Bangkok. Eligible patients included 21 women who had a histological diagnosis of breast cancer with more than 10 axillary lymph nodes involved. The patients first underwent modified radical mastectomy, followed by conventional doxorubicin containing adjuvant chemotherapy, before entering the treatment program. Peripheral blood stem cells were mobilized with cyclophosphamide and G-CSF and were harvested by leukapheresis. High dose chemotherapy consisted of cyclophosphamide 5,625 mg/m2, cisplatinum 165 mg/m2 and carmustine (BCNU) 600 mg/m2 were subsequently given, followed by infusion of the harvested peripheral blood stem cells. The median duration of cytopenia after transplantation was 8 days (range 7-12). The median expense for the transplantation, in addition to the cost of mastectomy and conventional chemotherapy, was 224,396 Baht (approximately US $5,350). Three out of the first four patients developed interstitial pneumonitis within three months after transplantation. There was one fatal case which was the only regimen related mortality. BCNU was then reduced to 450 mg/m2 and lung complications were markedly reduced afterwards. The median follow up time was 37 months with a median disease free survival of 38 months and overall survival of four years at 84%.

Adult↗

HER-2/neu overexpression as a poor prognostic factor for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous stem cell transplantation.

PURPOSE: High-dose chemotherapy with autologous stem cell transplantation (HDCT) produces a high tumor response rate for patients with metastatic breast cancer and have 20% long-term progression-free survival. Overexpression of HER-2/neu oncoprotein predicts outcome in patients with breast cancer given standard-dose chemotherapy. Therefore, we evaluated whether the HER-2/neu overexpression in the primary tumor predicts clinical outcome in patients with metastatic breast cancer given HDCT. EXPERIMENTAL DESIGN: A total of 236 patients were given standard-dose induction chemotherapy followed by stem cell collection; high-dose chemotherapy with cyclophosphamide, thiotepa, and carmustine; and stem cell infusion. HER-2/neu expression was assessed by immunostaining with anti-HER-2/neu e2-4001 monoclonal antibody in 63 patients. RESULTS: Clinical characteristics and survival were similar for patients with known and unknown HER-2/neu status. HER-2/neu was overexpressed in 22 of 63 tumors (35%). There was some tendency for HER-2/neu overexpression to be associated with the absence of estrogen or progesterone receptors. In considering the association of HER-2/neu expression with patient outcomes, HER-2/neu overexpression was associated with generally shorter overall survival (P = 0.02) and progression-free survival (P < 0.01), and this association persisted to a lesser extent after adjustment for differences in important prognostic factors between the two groups. CONCLUSION: We conclude that HER-2/neu overexpression may represent an additional prognostic factor for patients with metastatic breast cancer who undergo HDCT.

Antibodies, Monoclonal↗

Gateways to Clinical Trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate, nevirapine, nifedipine, NSC-683864; Oral heparin; Paclitaxel, peginterferon alfa-2b, phenytoin, pimecrolimus, piperacillin, pleconaril, pramipexole hydrochloride, prednisone, pregabalin, progesterone; Rasburicase, ravuconazole, reteplase, ribavirin, rituximab, rizatriptan, rosiglitazone maleate, rotigotine; Semaxanib, sildenafil citrate, simvastatin, stavudine, sumatriptan; Tacrolimus, tamoxifen citrate, tanomastat, tazobactam, telithromycin, tenecteplase, tolafentrine, tolterodine tartrate, triamcinolone acetonide, trimetazidine, troxacitabine; Valproic acid, vancomycin hydrochloride, vincristine, voriconazole, Warfarin sodium; Ximelagatran, Zidovudine, zolmitriptan.

Clinical Trials as Topic↗

Dose-intensive therapy for extensive-stage small cell lung cancer and extrapulmonary small cell carcinoma: long-term outcome.

Treatment for extensive-stage small cell lung cancer (ES SCLC) or extrapulmonary small cell carcinoma (EPSC) is typically palliative. We set out to determine progression-free survival (PFS) and overall long-term survival of ES SCLC and EPSC patients, physiologically aged < or = 60 years, responding to first-line chemotherapy followed by high-dose combination alkylating agents with hematologic stem cell support. Patients in first-line chemotherapy response underwent stem cell collection (marrow, peripheral blood progenitor cells, or both) followed by high-dose therapy with 1 of 2 regimens: CBP (cyclophosphamide, cisplatin, and carmustine) or ICE (ifosfamide, carboplatin, and etoposide) with or without etanidazole. Involved-field radiotherapy was given to selected patients with oligometastatic disease distributed in sites allowing for reasonable radiation ports, and prophylactic cranial radiotherapy was given upon recovery to patients in complete response (CR) or near-CR. A total of 36 patients were treated. Of 29 patients with ES SCLC, 6 (21%) had achieved CR, 18 near-CR, and 5 partial response prior to high-dose therapy. Of 7 patients with EPSC, 3 (43%) had achieved CR, 3 had achieved near-CR, and 1 had progression of disease prior to high-dose therapy. Thirteen ES SCLC patients received high-dose CBP. Of the remaining 23 patients with SCLC or EPSC, 17 were treated with ICE and 6 with ICE plus etanidazole, a hypoxic cell sensitizer. Treatment-related mortality was 11% (4 of 36 patients). For all patients, the median event-free survival (EFS) was 5 months. The 2- and 5-year survivals after intensification were 12% (95% confidence interval [CI], 5%-31%) and 9% (95% CI, 3%-27%), respectively. Of the 30 patients in or near CR prior to high-dose therapy, 5 remain continuously progression-free (2 ES SCLC, 3 EPSC) for a median of 55 months (range, 1-96 months) after high-dose therapy. By multivariate analysis, factors associated with more favorable EFS were the use of a more aggressive induction regimen (ICE), and the EPSC histology. These factors were also associated with more favorable overall survival. Other factors associated with more favorable overall survival were the use of short induction therapy (< or = 4 cycles) and younger age (<50 years). Except for high-dose ICE with etanidazole, the use of high-dose systemic therapy in ES SCLC and EPSC was associated with low treatment-related morbidity and mortality over the past 5 years. Late complications were infrequent, and most patients returned to full-time work and activity, barring disease recurrence. Nonetheless, few patients with ES SCLC have progression-free long-term survival. We conclude that high-dose therapy is not indicated as an approach for ES SCLC, except as part of an investigative trial. Conversely, 3 of the 7 patients with EPSC remain relapse-free (range, 1-96 months), warranting further phase II evaluation of this approach in this population.

Adult↗

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution.

Temozolomide is a new cytotoxic alkylating agent that has recently been approved in Portugal for the treatment of recurrent high-grade glioma. From September 1999 to March 2001, 16 patients with recurrent glioblastoma multiforme who had prior nitrosurea-based chemotherapy [procarbazine, carmustine, vincristine (PCV)] were given temozolomide 150-200 mg/m2/day for 5 days every 28-day cycle. The estimated 1-year survival rate was 16% and the median overall survival was 6.5 months. Despite the small sample size, the overall survival achieved with temozolomide was similar to that of other reports. These promising data suggest that randomized trials should be undertaken to assess its use in first-line therapy its inclusion in combined chemotherapy regimes and its effectiveness with concurrent radiotherapy.

Adult↗

Allogeneic stem cell transplantation in treatment of aggressive lymphomas: case series.

AIM: To assess the outcome of allogeneic stem cell transplantation in patients with aggressive lymphoma. METHODS: Between 1991 and 2002, 22 patients with aggressive lymphoma in advanced phase of the disease underwent allogeneic stem cell transplantation at the Division of Hematology, Zagreb University Hospital Center. Seventeen patients received stem cells from the bone marrow. Eighteen patients underwent total body irradiation and received cyclophosphamide for conditioning, whereas the rest of the patients received busulfan and cyclophosphamide (n=2) or chemotherapeutic protocol combining carmustine, melphalan, etoposide, and cytarabine (BEAM regimen) (n=2). All patients received cyclosporin and short methotrexate for the prophylaxis of graft-versus-host disease (GVHD). RESULTS: Three months after allotransplantation, 17 patients had complete remission, 3 patients had active disease, and the outcome in 2 patients was early death. Nine patients were alive and in complete remission for 4 to 124 months, whereas 13 patients died (8 because of disease progression and 3 because of GVHD and infection). The probability of overall survival at 4 years was 47%. CONCLUSION: Allogeneic transplantation is an effective therapy for advanced aggressive lymphoma. Because of high treatment-related toxicity and mortality, prospective trials are needed to asses the best time when to apply this treatment.

Adolescent↗

High-dose chemotherapy in small-cell lung cancer.

Small cell lung cancer (SCLC) is highly sensitive both to radiotherapy and chemotherapy. Given its high chemo sensitivity, even two decades ago, SCLC was one of the first malignancies deemed suitable for maximising the dose and dose intensity with the support of autologous bone marrow (ABMT). On the whole, results were disappointing and the procedure was practically abandoned. Nowadays some interest is again emerging due to improvements in supportive care, such as the availability of hematopoietic growth factors and the peripheral blood progenitor cells (PBPC). Data of 505 patients included in 26 studies were reviewed. About two thirds of these patients had LD (limited disease). Late intensification protocols were used in 311 patients who, however, represented only the 30% of the population initially given conventional chemotherapy. Of the patients not achieving complete remission (CR) after induction, high-dose induced a CR in 39% of the cases. The use of early intensification was reported in 8 studies including 194 patients. The CR rate was 51.5%. Overall, the probability of achieving the CR was 2-3 times higher in LD than in ED (extensive disease). Relapses occurred at the site of the primary in more than half of the cases, showing that the course of the disease was not modified by the use of high-dose chemotherapy. Toxic deaths occurred in 7% of the treated patients, without difference in the two treatment methods. Though the schedules were too variable to draw firm conclusions, the ICE (ifosfamide, carboplatin, etoposide) and the CBP (cyclophosphamide, cisplatin, carmustine) regimens apparently provided better results, with a 2-year survival rate of 30-50% in the LD subset. An european multicenter randomized trial is ongoing. At the present time high-dose chemotherapy is still to be considered experimental treatment, since major problems such as the selection of the patients, doses and timing of chemotherapy and radiotherapy remain unsolved.

Antineoplastic Combined Chemotherapy Protocols↗

Preliminary report of a phase I study of combination chemotherapy and humanized A33 antibody immunotherapy in patients with advanced colorectal cancer.

PURPOSE: In previous studies, humanized A33 (huA33) demonstrated modest antitumor activity in chemotherapy-resistant colorectal cancer patients. In addition, unexpected major tumor responses were observed in patients treated with a specific chemotherapy regimen [carmustine, vincristine, fluorouracil, and streptozocin (BOF-Strep)] administered after huA33 protocols. We designed the present Phase I, open label, cohort, dose-escalation study of huA33 and a fixed dose of BOF-Strep to (a) determine the maximum tolerated dose of huA33 immunotherapy administered with chemotherapy, (b) determine whether chemotherapy modifies huA33 immunogenicity, and (c) develop preliminary information regarding antitumor activity. EXPERIMENTAL DESIGN: Stage IV fluorouracil/leucovorin and irinotecan-refractory colorectal cancer patients (n = 16) received escalating weekly doses of huA33 (5-40 mg/m(2)) with BOF-Strep chemotherapy. RESULTS: Four patients requiring radiotherapy or surgery were removed early. Of 12 evaluable patients, grade 3 and 4 neutropenia (n = 2) and grade 3 thrombocytopenia (n = 1) were observed. Seven of 12 (58.3%) patients developed anti-huA33 activity. Three patients had radiographic partial responses for 7.5, 5.5, and 14 months with greater than 85% decline in serum carcinoembryonic antigen levels. One mixed response (4.5 months with a serum carcinoembryonic antigen decline of 38%) was also observed. CONCLUSIONS: huA33 can be safely combined with BOF-Strep chemotherapy. The present report provides compelling evidence supporting our previous observations of major antitumor activity with the combination of huA33 and BOF-Strep chemotherapy. huA33 is still immunogenic when administered with chemotherapy. Future studies to evaluate the immunogenicity of new huA33 antibodies and identify which drugs in the BOF-Strep regimen are critical for enhanced antitumor efficacy are planned.

Adult↗

Irinotecan: promising activity in the treatment of malignant glioma.

Patients with malignant glioma continue to have a dismal outcome. Those with glioblastoma multiforme, the most common type of malignant glioma, have a median survival of 40 to 60 weeks following diagnosis and only 16 to 24 weeks after recurrence. While standard therapy is surgery and external-beam radiotherapy, data indicate that chemotherapy improves the clinical outcome of some patients. Irinotecan (CPT-11, Camptosar) possesses significant activity against malignant glioma, and potentiation of this activity with combination partners, including the alkylator 1,2-bis(2-chloroethyl)-1-nitrosourea (carmustine, BCNU), is being evaluated in an ongoing phase II study. Also, the combination of irinotecan plus temozolomide (Temodar) has produced synergism in preclinical studies as well as encouraging responses in ongoing clinical trials. Other investigative directions include studies of irinotecan plus temozolomide and O6-benzylguanine (O6-BG) to assess the ability of O6-BG to maximize the therapeutic benefits of irinotecan combined with temozolomide.

Animals↗

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↗

Non-haematological toxicity limiting the application of sequential high dose chemotherapy in patients with advanced breast cancer.

A programme of repeated high dose chemotherapy for advanced breast cancer was developed using (1) cyclophosphamide 4 g/m2 followed by autologous peripheral blood stem cell (PBSC) collection; (2) three cycles of conventional dose chemotherapy; (3) high dose cyclophosphamide, cisplatin, and carmustine with PBSC rescue; and (4) high dose etoposide and melphalan with PBSC rescue. Fifteen eligible patients had advanced poor prognosis breast cancer either at initial diagnosis (one patient) or at relapse (14 patients). During the course of the protocol, there were three treatment related deaths, two patient withdrawals due to debilitating toxicity, five patient withdrawals due to disease progression, and one patient withdrawal due to inadequate collection of PBSC. The remaining four patients did not complete the planned protocol as the programme was terminated because of the unacceptable morbidity and mortality. They were treated with an alternative high dose chemotherapy protocol which was well tolerated. This study highlights the significant problems associated with a complex sequential high dose chemotherapy regimen. Cyclophosphamide mobilized PBSC infused following high dose chemotherapy enables rapid haematological recovery. However the non-haematological toxicity following high dose chemotherapy regimens is often severe and may limit the application of certain sequential high dose chemotherapy combinations in patients with breast cancer.

Adult↗

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↗

New drugs and combinations for malignant glioma.

A new chemotherapy agent and a method for local delivery of carmustine have recently been approved for the treatment of malignant glioma. However, the increase in survival remains modest at best with only a very select patients currently benefiting truly of these treatments. Combination regimen of different alkylating agents or prior O6-alkyltransferase depletion by O6-benzylguanine or continuous temozolomide administration schedules have shown some indication for increased activity. There is preclinical rational for combining temozolomide with radiotherapy and the initial results of a phase II clinical trial were promising. Several new cytotoxic agents are currently in clinical trials in patients with recurrent glioma. More importantly, targeted therapy and antiangiogenic agents have entered the clinical development phase also for patients with glioblastoma and anaplastic astrocytoma. The optimal timing of administration of non-cytotoxic substances and their integration into the currently available treatments remains a challenge. Novel study designs and identification of surrogate markers are necessary in order to make rapid and clinically meaningful progress. This review summarises the currently available evidence of activity of the recently approved drugs against malignant glioma and mentions also agents which have failed to demonstrate a significant antitumour activity. Study endpoints are critically discussed. Combination regimens with other agents and radiation therapy are reviewed. The rational for using antiangiogenic drugs in selected ongoing trials is discussed.

Journal Article↗

Long term survival in a patient with multiple myeloma. A case report with review of literature.

A 37 year old man with symptomatic multiple myeloma diagnosed in April 1968 presented with generalised bony pains, extensive skeletal osteolytic lesions, monoclonal gammopathy and 90 percent atypical plasma cells in the marrow. He was given cyclophosphamide for six months with minimal response and then initiated on melphalan for one year. He was asymptomatic for 15 years thereafter and presented again in 1985 with a relapse of the disease. Over the next four years he was given various combinations of chemotherapy including cyclophosphamide, vincristine, melphalan and carmustine. He responded well on two more occasions only to relapse again. Recently, he has developed a symptomatic relapse with 36 percent plasma cells. This case report highlights the fact that there is a subset of patients with myeloma who survive beyond ten years, but remain symptomatic and respond slowly to chemotherapy.

Adult↗

High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies.

High-dose etoposide has been added to total body irradiation, cyclophosphamide, carmustine, or busulfan in preparatory regimens for allogeneic or autologous bone marrow transplantation for patients with leukemia, Hodgkin's disease, lymphoma, or multiple myeloma. The treatment results are encouraging, indicating that etoposide may be a valuable addition to the previously established regimens. Etoposide should be incorporated into collaborative, prospective trials to define its ultimate role in bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy during first complete remission in adult patients with poor-risk aggressive lymphoma: a pilot study.

Twenty consecutive patients with poor-risk aggressive lymphoma who at presentation either had elevated serum lactic dehydrogenase level (LDH) and any one of the other poor-prognostic features: bulky mass greater than or equal to 10 cm, advanced stage III or IV, and greater than or equal to 2 extranodal sites, or normal LDH level and all other three features, underwent high-dose chemo/radiotherapy followed by unmanipulated autologous bone marrow transplantation (BMT) during their first complete remission. Eighteen had B-cell lymphoma and 2 had T-cell lymphoma. Eleven patients had high-grade (7 immunoblastic, 3 small noncleaved, non-Burkitt's, and 1 Burkitt's) and 9 had diffuse large cell lymphoma. All patients had achieved a complete remission following conventional chemotherapy. Four patients had also received involved field radiotherapy to areas of bulky disease. The preparative regimen consisted of high-dose etoposide 60 mg/kg and cyclophosphamide 100 mg/kg in combination with fractionated total body irradiation (FTBI) 1,200 cGy (15 patients), or single-dose TBI 750 cGy (2 patients), or carmustine 450 mg/m2 (3 patients). All patients tolerated the treatment well and achieved complete hematologic recovery. Three patients have relapsed at days 79, 196, and 401 after transplantation. Seventeen patients (84%) are alive and relapse-free with a median follow-up of 34 months (range 2 to 54). We conclude that high-dose chemo/radiotherapy followed by autologous BMT can be given as consolidation therapy during first remission in these patients with minimal transplant-related toxicity.

Adult↗

Disposition of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving high-dose chemotherapy and autologous bone marrow support.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) produces dose-related therapeutic and toxic effects; however, relationships between its pharmacokinetics and pharmacodynamics have not been extensively evaluated. The following studies were undertaken to investigate patterns in the disposition of rHuGM-CSF administered after high-dose chemotherapy (cyclophosphamide, cisplatin, carmustine) and autologous bone marrow support. Continuous 14 or 21 day intravenous infusions or daily 4-hour infusions were studied at doses of 1.2 to 19.2 micrograms/kg/d. GM-CSF was measured by an enzyme-linked immunosorbent assay from serum and urine samples collected throughout drug administration. Pharmacokinetic parameters were determined by compartmental (4-hour infusions) or noncompartmental methods (continuous infusions). GM-CSF was rapidly eliminated from the serum. Average systemic exposure increased with dose, although wide interpatient variability was evident. Approximately one half of the patients receiving continuous infusions demonstrated increasing GM-CSF clearance that corresponded to the appearance of white blood cells in the periphery. Conversely, clearance decreased in those experiencing renal dysfunction during the infusion. The percentage of a GM-CSF dose found in 24-hour urine collections was substantially reduced in the latter group. A subset of patients who developed renal dysfunction also experienced significant hypotension. Rapidly increasing serum GM-CSF concentrations corresponded to the hypotensive episodes. GM-CSF serum concentration monitoring may be useful for evaluation of therapeutic and toxic effects in patients receiving high-dose chemotherapy with autologous bone marrow support.

Antineoplastic Combined Chemotherapy Protocols↗

[Current treatment methods in skin tumors].

Modern aspects of treatment for malignant melanoma, basalioma and cutaneous lymphomas are reviewed. Cytokines have been proposed as immunostimulants in adjuvant therapy (destruction of residual tumor) for malignant melanoma or at high doses for treatment of metastatic melanoma. Basalioma is the most common tumor of the skin, prone to recurrence because of its iceberg-like subclinical growth-pattern. Micrographic surgery is best adapted to this growth behaviour by following the extent of the tumor in all directions by special histopathologic techniques thus permitting radical excision. Primary lymphomas of the skin although rare (1 in 100,000 per year) prevail and cumulate because of the long course over years and decades. New treatment avenues have opened by topical use of phospholipids and cytostatic drugs i. e. carmustine (BCNU).

Administration, Topical↗