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PubMed1990

New carbon dioxide-independent basal growth medium for culture of diverse tumor and nontumor cells of human and nonhuman origin.

A eukaryotic growth medium (Program Development Research Group Basal Growth Medium) was developed for CO2-independent maintenance and propagation of human and nonhuman tumor cell lines representing diverse histologies (e.g., cancers of the brain, colon, lung, ovary, and kidney, as well as leukemia and melanoma). It was also shown to be suitable for the maintenance and propagation of nontumor cells of human and nonhuman derivation. The medium derives its buffering capacity primarily from beta-glycerophosphate, exhibits a stable physiologic pH of 7.3-7.4, and is optimized to facilitate growth in atmospheric CO2. It is also useful in cellular growth and cytotoxicity assays based on either the metabolic reduction of tetrazolium reagents or protein staining. The 50% inhibitory concentration values obtained with carmustine, doxorubicin, and tamoxifen in cell lines maintained in the new medium under atmospheric CO2 were closely comparable to those obtained with these drugs against cells maintained in RPMI-1640 under a 5% CO2 environment.

Animals↗
PubMed1993

Intensive combined modality therapy for limited-stage small-cell lung cancer.

BACKGROUND: Conventional-dose chemotherapy for small-cell lung cancer has resulted in high response rates but rarely in a cure. The addition of thoracic radiotherapy (chemoradiotherapy) has improved survival for patients having limited disease, resulting in a median survival of 14-18 months. Previous trials evaluating high-dose chemotherapy and autologous bone marrow transplantation have demonstrated enhanced complete response rates without documenting overall survival benefit. PURPOSE: The purpose of this phase II trial was to determine the disease-free and overall survival, toxic effects, and relapse patterns in patients with limited small-cell lung cancer who were in partial or complete response to first-line conventional-dose chemotherapy and then received intensive systemic combined modality therapy. METHODS: Adults with stage III small-cell lung cancer who had achieved at least a partial response to conventional-dose induction chemotherapy were treated with high-dose cyclophosphamide, cisplatin, and carmustine combined with autologous bone marrow transplantation. Cumulative doses of the three drugs were 5625, 165, and 480 mg/m2, respectively. After recovery, patients received thoracic radiotherapy (50-60 Gy in 25-30 fractions over 5-6 weeks) and cranial radiotherapy (30 Gy in 15 fractions during 3 weeks). RESULTS: Of 19 patients in the study, six had achieved complete response, eight had a greater than 90% reduction in tumor size, and five had a 50%-90% reduction in tumor size. After high-dose therapy, 15 of the 19 were in complete response. Overall, median time to treatment failure after high-dose therapy was 12 months. Overall survival was 73% (95% confidence interval [CI] = 42%-89%) at 1 year and 53% (95% CI = 22%-77%) at 2 years. Of the 14 patients in or near complete response before high-dose therapy, 10 remain disease free with no further chemotherapy a median of 15 (4-69+) months after therapy. Actuarial 2-year disease-free survival is 57% (95% CI = 20%-82%). One patient died of Candida sepsis. Morbidity was low, and most patients returned to full-time work. With the exception of herpes zoster, there were no complications more than 3 months after high-dose therapy. CONCLUSIONS: The majority of the patients in this study are experiencing prolonged and unmaintained disease-free survival. Our findings suggest that patients in or near complete response before high-dose therapy have the most favorable prognosis. IMPLICATIONS: A randomized comparison between this approach and conventional-dose therapy is planned to define the utility of dose intensification with autologous bone marrow transplantation in the treatment of patients with limited-stage small-cell lung cancer who are in or near complete response.

Actuarial Analysis↗
PubMed1995

Hypersensitivity reactions to chemotherapy agents in patients receiving chemoimmunotherapy with high-dose interleukin 2.

BACKGROUND: Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given. PURPOSE: In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy. We therefore decided to examine these hypersensitivity reactions in detail. METHODS: During the period of March 1993 through February 1994, 31 patients with metastatic melanoma were treated either by chemotherapy (dacarbazine, cisplatin, and tamoxifen) or by chemoimmunotherapy (the same drug regimen plus interferon alfa and high-dose IL-2). Twelve patients were treated in a non-randomized pilot study, with six receiving chemotherapy and six receiving chemoimmunotherapy. The six patients who received chemotherapy also received carmustine (BCNU). Nineteen subsequent patients were treated in a prospective, randomized study to compare the two therapeutic approaches. In total, 15 of the 31 patients were treated by chemotherapy alone, and 16 were treated by combination chemoimmunotherapy. Overall, the patients in the two groups were balanced in terms of age, sex, and stage of disease. RESULTS: Ten of 16 chemoimmunotherapy patients exhibited type I hypersensitivity reactions during chemotherapy administration, ranging from pruritus, erythema, and edema to hypotension with hemodynamic instability that required pressor therapy. None of the 15 patients on the chemotherapy regimen exhibited hypersensitivity reactions. All patients in the chemoimmunotherapy group gained weight and had elevated white blood cell and eosinophil counts during chemotherapy; these effects were more prominent in those with hypersensitivity reactions. CONCLUSIONS: Hypersensitivity reactions occurred within several hours after chemotherapy administration in patients who had previously received one to two cycles of high-dose IL-2, suggesting that prior IL-2 therapy sensitized patients to cisplatin or dacarbazine. This is the first report of IL-2-induced hypersensitivity to chemotherapy agents.

Adult↗
PubMed2001

Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized phase III EORTC study.

BACKGROUND: The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival. METHODS: Patients aged 15-65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). All statistical tests are two-sided. RESULTS: From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low-intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results. CONCLUSIONS: Standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low-intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.

Adolescent↗
PubMed2002

Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience.

A phase II study of irinotecan (CPT-11) was conducted at Duke University Medical Center, Durham, NC, to evaluate the activity of this agent in children with high-risk malignant brain tumors. A total of 22 children were enrolled in this study, including 13 with histologically verified recurrent malignant brain tumors (glioblastoma multiforme [GBM] 4, anaplastic astrocytoma 1, ependymoma 5, and medulloblastoma/primitive neuroectodermal tumor 3), 5 with recurrent diffuse pontine glioma, and 4 with newly diagnosed GBM. All patients with recurrent tumor had prior chemotherapy and/or irradiation. Each course of CPT-11 consisted of 125 mg/m ( 2 ) per week given i.v. for 4 weeks followed by a 2-week rest period. Patients with recurrent tumors received therapy until disease progression or unacceptable toxicity. Patients with newly diagnosed tumors initially received 3 cycles of treatment to assess tumor response and then were allowed radiotherapy at physician's choice; patients who demonstrated a response to CPT-11 prior to radiotherapy were allowed to continue the drug after radiation until disease progression or unacceptable toxicity. A 25% to 50% dose reduction was made for grade III-IV toxicity. Responses were assessed after every course by gadolinium-enhanced MRI of the brain and spine. Twenty-two patients received a median of 2 courses of CPT-11 (range, 1-16). Responses were seen in 4 of 9 patients with GBM or anaplastic astrocytoma (44%; 95% confidence interval, 11%-82%) (complete response in 2 patients with recurrent GBM lasting 9 months and 48+ months; partial response in one patient with a newly diagnosed midbrain GBM lasting 18 months prior to radiotherapy; and partial response lasting 11 months in 1 patient with recurrent anaplastic astrocytoma), 1 of 5 patients with recurrent ependymoma (partial response initially followed by stable disease lasting 11 months), and none of 5 patients with recurrent diffuse pontine glioma. Two of 3 patients with medulloblastoma/primitive neuroectodermal tumor had stable disease for 9 and 13 months. Toxicity was mainly myelosuppression, with 12 of 22 patients (50%) suffering grade II-IV neutropenia. Seven patients required dose reduction secondary to neutropenia. CPT-11, given in this schedule, appears to be active in children with malignant glioma, medulloblastoma, and ependymoma with acceptable toxicity. Ongoing studies will demonstrate if activity of CPT-11 can be enhanced when combined with alkylating agents, including carmustine and temozolomide.

Adolescent↗
PubMed1995

Prolonged disease-free survival following surgical debulking and high-dose cisplatin/doxorubicin in a patient with bulky metastases from giant cell tumor of bone refractory to "standard" chemotherapy.

A 32-year-old man developed multiple pulmonary metastases from a giant cell tumor of bone. His metastases failed to respond to several chemotherapy regimens (high-dose methotrexate with folinic acid plus doxorubicin 90 mg/m2; cyclophosphamide + bleomycin + actinomycin D; mitoxantrone + dacarbazine; and cisplatin 110 mg/m2). He underwent surgical resection (incomplete) of > 1 kg of tumor from his right lung in March 1985, followed by chemotherapy with menogaril (to which he did not respond). In August 1985, he underwent surgical resection (again, incomplete) of > 1 kg of tumor from his left lung. At the time of surgery, the left and right lung tumors differed histopathologically, with giant cell tumor present in the right lung and sarcoma in his left lung. He received carmustine in October 1985 and mitomycin C in December 1985 without response. His multiple bilateral lung metastases had again become quite large by September 1986. At that time, he received doxorubicin 90 mg/m2 plus cisplatin 120 mg/m2, and for the first time experienced tumor reduction (minor response). He underwent a subtotal resection of right lung and chest wall metastases in December 1986, and underwent subtotal resection of left lung metastases in January 1987. Grossly visible residual tumor was left behind on both sides at the time of surgery, although none was apparent on chest radiograph. He received a final chemotherapy treatment with doxorubicin 90 mg/m2 plus cisplatin 120 mg/m2 on February 2, 1987. He remained free of evidence of residual or recurrent tumor at the time of last followup in February, 1994.

Adult↗
PubMed1998

Paclitaxel as the initial treatment of multiple myeloma: an Eastern Cooperative Oncology Group Study (E1A93).

The authors assess the activity and toxicity of paclitaxel in previously untreated patients with multiple myeloma. Eighteen patients with previously untreated multiple myeloma were enrolled. Paclitaxel was given in a dose of 250 mg/m2 by a continuous intravenous infusion for 24 hours every 21 days for four cycles. All patients received granulocyte colony stimulating factor in a dose of 5 microg/kg each day until the absolute neutrophil count was 10,000/mm3. All patients were evaluated after four cycles. Four (29%) objective responses were observed in the 14 eligible patients. No complete responses occurred. Three lethal toxicities were observed, two were the result of neutropenic sepsis. Sixty-one percent of patients experienced some type of severe nonhematologic toxicity. Patients who received four cycles of paclitaxel were given further treatment at the discretion of the investigator. The median survival of all eligible patients was 2.8 years, which is comparable with the median survival with melphalan and prednisone of 2.3 years or vincristine, carmustine, melphalan, cylophosphamide, and prednisone of 2.4 years. Paclitaxel in the dosage used in this study has prohibitive toxicity. The four (29%) responses in 14 evaluable untreated patients indicates that paclitaxel is active in the treatment of multiple myeloma. No complete remissions were recorded. Further studies using paclitaxel in a smaller dose, in combination with other agents, or using one of the paclitaxel analogs may be useful in the treatment of multiple myeloma.

Adult↗
PubMed1994

Development of resistance to 9-nitro-camptothecin by human leukemia U-937 cells in vitro correlates with altered sensitivities to several anticancer drugs.

We have recently reported that exposure of human leukemia U-937 cells to progressively increasing concentrations of 9-nitro-camptothecin (9NC) resulted in cell sublines exhibiting various levels of resistance to 9NC. Here, we report responses of wild-type (U-937/wt) and 9NC-resistant (U-937/CR) cells to various anticancer drugs used extensively in cancer chemotherapy. U-937/CR cells were more sensitive than U-937/wt cells to several commonly used drugs of diverse origin including the topoisomerase II-directed drugs amsacrine, etoposide and daunorubicin; the vinca alkaloid vincristine; and the antimetabolite methotrexate. No responses were induced by carmustine in either cell type, whereas similar responses were induced by cytarabine. The sensitivity to the drugs was investigated by monitoring cell proliferation, by determining cell cycle perturbations assessed by flow cytometry analysis of DNA content and by microscopy of stained cells. The results in this report indicate that development of 9NC resistance by the U-937 cells is accompanied by increased sensitivities to other anticancer drugs in vitro and very likely in vivo.

Antineoplastic Agents↗
PubMed1995

Schedule-dependent enhancement of antitumor activity of ethyldeshydroxy-sparsomycin in combination with classical antineoplastic agents.

The efficacy of the protein synthesis inhibitor ethyldeshydroxy-sparsomycin (EDSM) as a biochemical response modifier of several antitumor agents against L1210 leukemia and B16 melanoma is described. Seven drugs with different intracellular targets were selected for this combination study. Tumor implantation and drug treatment were both i.p., and the time interval between the administration of EDSM and the cytostatic agent was varied. Our results show that in the B16 tumor model EDSM is not able to potentiate any of these drugs, whereas antagonism is seen in combination with doxo-rubicin (DX). In the L1210 tumor model, however, no loss of activity is seen for this specific combination. The effect of the combination of cytosar (Ara-C), 5-fluorouracil (5-FU) or vincristine (VCR) with EDSM in the L1210 model is strongly time interval dependent. Loss of 5-FU antitumor activity is seen when EDSM is given 3 or 24 h after 5-FU; however, no effect is observed when EDSM is given 6 h after 5-FU. Enhancement of the 5-FU activity is not noticed. The VCR activity is potentiated when EDSM is given at least 6 h after VCR administration, which increases the antitumor response from 32 to > 60 days and the percentage survivors from 33 to 83% (p = 0.04). In combination with Ara-C, potentiation of antitumor activity is seen only when EDSM is given 24 h after Ara-C, which increases the antitumor response from 32 to > 55 days and the percentage survivors from 11 to 50% (p = 0.008). No modulatory effects are found when EDSM is combined with carmustine or DX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Altered immunologic reconstitution after standard-dose chemotherapy or high-dose chemotherapy with autologous bone marrow support.

Altered immunologic reconstitution is observed in patients treated with high-dose chemotherapy consisting of cyclophosphamide, cisplatin, and carmustine, melphalan, or etoposide with autologous bone marrow support, and it is similar to that seen in patients treated with high-dose chemoradiotherapy and allogeneic bone marrow transplantation. A decrease in the absolute number and percentage of B cell and CD4 antigen-positive cells and an increase in the absolute number and percentage of CD8 and Ia antigen-positive cells occur along with a decrease in the CD4/CD8 ratio that persists for 6-12 months after high-dose chemotherapy and autologous bone marrow support. These changes have been associated with four serious infectious episodes usually seen only in immunocompromised patients. The above changes were not seen in patients treated with high-dose busulfan, a drug that has relatively specific effects on granulocytes. It is postulated that these alterations result from effects of chemotherapy on the residual lymphocytes or on the environment of repopulating lymphocytes. Functional studies of lymphocyte populations during immunologic reconstitution after standard-dose combination chemotherapy and high-dose chemotherapy with autologous bone marrow support are needed.

Antibodies, Viral↗
PubMed1998

Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma.

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.

Adolescent↗
PubMed2005

Research on the anti-tumour effect of steroid lactam alkylator (NSC-294859) in comparison with conventional chemotherapeutics in malignant melanoma.

Evidence indicating that hybrid steroid compounds of anti-cancer agents produce reduced toxicity, significantly lower than the cytotoxic components alone, and increased anti-cancer activity has prompted the design and development of such steroids, mostly alkylating esters. We investigated the in-vitro and in-vivo activity of a homo-aza-steroidal alkylating ester (HASE), in comparison with dacarbazine (DTIC), cisplatin (CPDD), carmustine (BCNU) and semustine (MeCCNU), in the treatment of malignant melanoma. Cytotoxicity was assessed in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using a panel of six human malignant melanoma cell lines, with or without the presence of rat liver microsome assay. B16 melanoma-bearing mice were used to evaluate in vivo the anti-tumour activity of the tested compounds. In all cases of in-vitro screening, HASE displayed a significantly higher (P<0.0001) cytostatic and cytotoxic effect than DTIC, BCNU and MeCCNU, but produced significantly lower (P<0.0001) activity than CPDD. HASE exhibited a significantly smaller range than CPDD between concentration levels that produced growth arrest and those that induced a cytotoxic effect against melanoma cells in vitro. The anti-tumour activity of HASE in B16 melanoma-bearing mice, as determined by tumour growth rate inhibition (<42%) and percentage survival prolongation (treated versus control, 167%), was significantly superior (P<0.001) to that achieved by DTIC, BCNU and MeCCNU and was equal to that of CPDD. HASE exhibited a toxicity similar to that of DTIC, BCNU and MeCCNU, but significantly lower than that of CPDD. It can be concluded that HASE displays significant in-vitro and in-vivo activity in the treatment of melanoma.

Animals↗
PubMed1996

Evaluation of the relative cytotoxic effects of anticancer agents in serum-supplemented versus serum-free media using a tetrazolium colorimetric assay.

Most cell culture and in vitro drug sensitivity assays utilize serum-supplemented media (SSM). However, fully defined serum-free media (SFM) offer several advantages and are being used increasingly for initiation and maintenance of cell cultures. Because serum inhibits the in vitro cytotoxicity of certain antineoplastic agents, we investigated the inter-relationships between medium type, cell proliferation and cytotoxic effect. Twenty-four human lung cancer cell lines were tested with nine anticancer agents in both media types. A semi-automated tetrazolium (MTT) colorimetric assay was used for assaying cell survival. Cell lines initiated and maintained in SFM preferentially proliferated in that medium type or proliferated equally well in both media types. In contrast, cell lines established in SSM varied considerably in their medium of preference. There appeared to be a direct correlation or trend between cell proliferative rate and cytotoxicity of all drugs with the possible exceptions of methotrexate and carmustine. In general, the cell lines were more sensitive to anticancer agents when they were exposed in the culture medium in which they preferentially proliferated. Therefore, to determine the influence of culture media on cytotoxicity, we analyzed the data only from lines that replicated equally efficiently in both media. After correction for cell proliferative rate, SSM had a negative effect on the cytotoxic action of some drugs (especially methotrexate, 5-fluorouracil and, to a lesser extent, mitomycin-C). Our results demonstrate that fully defined SFM may be suitable for initiating cell lines and for use in in vitro cytotoxicity assays for selection of individualized therapy or for screening of new anti-neoplastic agents, and thus may increase the number of antineoplastic agents that can be tested satisfactorily.

Antineoplastic Agents↗
PubMed2005

Successful bone marrow transplantation for life threatening xanthogranuloma disseminatum in neurofibromatosis type-1.

A 2-yr and 9-month-old female patient with neurofibromatosis type-1 presented with hepatomegaly, anemia, thrombocytopenia, and croupy cough and diagnosed with xanthogranuloma disseminatum (XD). She failed chemotherapy consisting of steroids, 6-mercaptopurine and methotrexate. A partial response to HLH-94 therapy that included etoposide and cyclosporine A was initially observed. However, she continued to have significant organ dysfunction without further improvement at 6 months of therapy. She then received matched unrelated donor bone marrow transplantation (BMT) following carmustine, etoposide, cytarabine and melphelan conditioning with complete resolution of symptoms. BMT is an option in therapy-resistant, life threatening XD cases.

Bone Marrow Transplantation↗
PubMed2006

Narrowband UVB phototherapy for early-stage mycosis fungoides: evaluation of clinical and histopathological changes.

BACKGROUND: Early-stage (IA, IB, IIA) mycosis fungoides (MF) has long been treated with various agents including topical potent steroids, nitrogen mustard, carmustine, oral psoralen plus UVA (PUVA), broadband UVB, electron-beam radiotherapy, interferon-alpha and retinoids. However, each of these modalities is associated with various side-effects. Narrowband UVB (NB-UVB) therapy has the same effect but is safer to use than the other methods. OBJECTIVE: Our purpose in this prospective study was to determine the effects of NB-UVB in early-stage MF both clinically and histopathologically. MATERIALS AND METHODS: Twenty-three patients (20 men, three women, aged 27-78 years) with clinically and histologically confirmed MF were enrolled. Patients received NB-UVB therapy three times a week. Clinical and histological responses, cumulative doses, total number of treatments, side-effects and duration of remission period were noted. RESULTS: Six patients had stage IA MF, 15 patients stage IB and two patients stage IIA. Eighteen patients had patch stage and five patients had plaque stage histopathologically. All of the patients in the patch group had a complete response (CR). In the plaque group, three patients (60%) had a CR and two (40%) had partial (PR) or no clinical response (NR). The clinical response between patch and plaque groups was statistically significant. Regarding the histopathological findings, 17 (94.4%) had complete clearing and only one (5.6%) patient had a partial improvement in the patch group. In the plaque group, one (20%) patient had complete clearing and four (80%) patients had partial or no improvement. The difference between the two groups was statistically significant. In the patch group, the mean cumulative dose was 90.15 J/cm(2) and the mean number of treatments was 35.33. In the plaque group, the mean cumulative dose was 90.67 J/cm(2) and the mean total number of treatments was 39.40. The differences were not statistically significant, either between the mean cumulative dose or the mean number of treatments. The mean duration of follow-up was 10.87 months (range 1-25 months). Only one of the patients had a relapse. CONCLUSIONS: NB-UVB therapy for patients with early-stage MF is an effective and safe treatment with the effect lasting for months. We suggest that clinical clearance correlates with histological improvement except for patients in the plaque stage.

Adult↗
PubMed2006

A prospective PET study of patients with glioblastoma multiforme.

OBJECTIVE: To study the post-surgical metabolic and structural cerebral changes in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: We examined ten patients prospectively with newly diagnosed GBM. All patients were primarily treated with surgery, followed by chemotherapy (carmustine, cisplatine and etoposide) and radiotherapy. Positron emission tomography (PET) was used to measure tumor- and cerebral metabolism. CT or MRI was used to estimate tumor volume by measurements of tumor area. RESULTS: Tumor metabolism was not increased during chemotherapy (P = 0.71), but increased during radiotherapy (P = 0.01). CT/MRI showed similar results with no increase in tumor area during chemotherapy (P = 0.33) but increase during radiotherapy (P = 0.002). During the entire study, tumor metabolism and area increased evenly (P = 0.01). CONCLUSIONS: Our study did not show a gain of PET compared with structural imaging in the prospective evaluation of GBM. We found a difference in metabolic increase and tumor growth between the two treatment regimens, although this finding has limited relevance due to the design of the study.

Adult↗
PubMed1988

Multiple myeloma in central and northern Norway 1981-1982: a follow-up study of a randomized clinical trial of 5-drug combination therapy versus standard therapy.

In a randomized study of 92 previously untreated patients with multiple myeloma, the intention was to document the possible beneficial effect of combination chemotherapy including vincristine, carmustine, alkylating agents and prednisone, as compared to conventional therapy with melphalan and prednisone. Major prognostic factors did not differ significantly between the treatment groups. With the 2-drug therapy and 5-drug combination therapy, 48 and 54% of the patients achieved remission, respectively. Median survival for patients treated with the 2-drug regimen and 5-drug regimen was 29 and 33.5 months, respectively. No significant difference was found between the survival curves for stage III patients treated with the two regimens. After 12 months, patients who had achieved remission were randomized to have treatment discontinued or to have maintenance treatment. The numbers of relapses, remission duration and survival of the two groups were similar.

Actuarial Analysis↗
PubMed1989

Melphalan/prednisone versus drug combinations for plasma cell myeloma.

Reports of 13 prospective, randomized clinical trials comparing standard treatment with melphalan and prednisone (MP) versus various drug combinations in the treatment of myeloma patients are presented. These studies reveal that patients with Durie-Salmon Stage III disease respond significantly more frequently to MP and drug combinations than those with Stage I and II. Drug combinations may be more effective in inducing objective responses. The response rates were significantly better for the drug combinations in 3 of the 13 comparisons. There was little evidence that either form of treatment was superior in prolonging survival, for in one study the patients treated with a drug combination lived significantly longer than those treated with MP, while in another the reverse was true, and there was no difference in the survival of the two groups in the remaining 11 studies. In the Vth MRC myelomatosis trial, patients treated with a combination of adriamycin, carmustine, cyclophosphamide and melphalan are living significantly longer than those treated with melphalan alone, and this survival advantage persists after correction for the most important prognostic factor, beta 2 microglobulin. Attempts to increase the intensity of treatment by using syngeneic, allogeneic or autologous marrow transplantation to rescue patients following otherwise lethal chemoradiotherapeutic treatments, have not yet demonstrated conclusively that the myeloma clone can be eliminated by this form of treatment.

Antineoplastic Combined Chemotherapy Protocols↗