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At least 973 records · Page 54Linked to original sources
PubMed1993

Combination or mild single agent chemotherapy for advanced breast cancer? CMF vs epirubicin measuring quality of life.

Forty patients with advanced breast cancer, randomised to receive CMF or weekly low dose Epirubicin, were evaluated by UICC criteria of response and WHO toxicity criteria, in addition to three QoL instruments: the 'Qualitator' daily diary card, 4 weekly Nottingham Health Profile (NHP) and Linear Analogue Self-Assessment (LASA). Response rates were 58% for CMF and 29% for epirubicin (chi 2 = 3.51, 1 d.f., P > 0.05). Median time to treatment failure was 24 weeks for CMF, 7 weeks for epirubicin (P < 0.05) but survival was similar in both groups. Survival was better for responders than for non-responders (medians 87 and 30 weeks, P = 0.02). CMF caused more objective alopecia (P < 0.001), nausea and vomiting (P < 0.001) and haematological toxicity (P < 0.02). However, QoL measures only recorded a significant difference in energy and pain, influenced primarily by the non-responders in each treatment group but with no difference in overall global scores. Scores for responders, irrespective of treatment, were better to start with (LASA P = 0.001); at 12 weeks, scores had improved (Qualitator P < 0.05; NHP P < 0.05). Scores in non-responders showed no change. In this small study aggressive chemotherapy gave better response and similar survival without impairing Quality of life overall. Detailed QoL measurement should be integral to all cancer chemotherapy trials.

Adult↗
PubMed1996

Initial prognostic factors in small-cell lung cancer patients predicting quality of life during chemotherapy. Swiss Group for Clinical Cancer Research (SAKK).

The question of whether initial prognostic factors in small-cell lung cancer patients have a predictive value for patients' quality of life (QL) during chemotherapy is addressed in the context of a randomised clinical trial comparing early and late alternating chemotherapy (SAKK protocol 15/84). The relative impact of initial tumour stage and performance status, previous weight loss, sex and age on patient-rated QL was analysed over six chemotherapy cycles in 124-130 patients (according to available QL data) with more than 400 questionnaires. Fatigue/malaise, personal functioning, emotional and general well-being were prospectively selected as QL indicators. Predefined summary measures (average QL score over chemotherapy cycles, 'minimum', 'maximum' and 'final' improvement) were analysed separately by scale in various patient groups. General linear models adjusted for treatment arm and response were used to confirm the univariate findings. Within the overall sample, the average QL scores over six cycles were predicted by initial prognostic factors. Patients with poor prognostic factors reported worse QL. Within a limited sample (with baseline QL), patients with poor prognostic factors reported worse QL at baseline and greater improvement under treatment. Graphical comparison of QL patterns over cycles showed permanent discrimination by levels of prognostic factors. The impact of initial prognostic factors was consistently confirmed in the three analyses. Levels of performance status and weight loss best discriminated QL. Initial tumour stage, performance status and previous weight loss can predict QL in small-cell lung cancer during chemotherapy, even after controlling for response to treatment. Our results may contribute to clinical decision-making with regard to the intensity of chemotherapy and QL outcome, especially in patients with extensive disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Genetic and metabolic predictors of chemosensitivity in oligodendroglial neoplasms.

The -1p/-19q genotype predicts chemosensitivity in oligodendroglial neoplasms, but some with intact 1p/19q also respond and not all with 1p/19q loss derive durable benefit from chemotherapy. We have evaluated the predictive and prognostic significance of pretherapy (201)Tl and (18)F-FDG SPECT and genotype in 38 primary and 10 recurrent oligodendroglial neoplasms following PCV chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII and was associated with response (Fisher-Exact: P=0.000) and prolonged progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank: P=0.0048). Response was unrelated to metabolism, with tumours with high or low metabolism showing response. Increased (18)F-FDG or (201)Tl uptake predicted shorter progression-free survival (PFS) in the series (log-rank: (201)Tl P=0.0097, (18)F-FDG P=0.0170) and in cases with or without the -1p/-19q genotype. Elevated metabolism was associated with shorter OS in cases with intact 1p/19q (log-rank: (18)F-FDG P=0.0077; (201)Tl P=0.0004) and shorter PFS in responders (log-rank: (18)F-FDG P=0.005; (201)Tl P=0.0132). (201)Tl uptake and 1p/19q loss were independent predictors of survival in multivariate analysis. In this initial study, (201)Tl and (18)F-FDG uptake did not predict response to PCV, but may be associated with poor survival following therapy irrespective of genotype. This may be clinically useful warranting further study.

Adult↗
PubMed1999

The minimum CD34 threshold depends on prior chemotherapy in autologous peripheral blood stem cell recipients.

We analysed 57 patients with non-myeloid malignancies who received a non-purged autologous PBSCT. All had similar mobilisation and conditioning regimens. A high prior chemotherapy score and the number of chemotherapy lines used (P = 0.015 and P = 0.01, respectively) were adverse predictors of CD34 cell yields. Lower CD34 values (P = 0.002) were seen in patients treated with potent stem cell toxins (BCNU, melphalan, CCNU and mustine), designated toxicity factor 4 agents (TF4). All patients infused with grafts containing CD34 cell doses between 1.0 and 2.0 x 10(6)/kg (range 1.25-1.90) engrafted by day 51. The only variable associated with slow platelet recovery was exposure to TF4 (P = 0.007). The majority of patients with CD34 >1.0 x 10(6)/kg achieved rapid and sustained engraftment and the only predictive factor of delayed recovery is prior exposure to stem cell toxins. Potential PBSCT candidates should if possible avoid first line and salvage chemotherapy containing TF4 drugs. We therefore advocate a minimum CD34 threshold of >1.0 x 10(6)/kg in patients without extensive prior chemoradiotherapy, and > or = 2.0 x 10(6)/kg in all other patients.

Adolescent↗
PubMed2001

Adenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent CCNU.

Due to minimal treatment success with surgery, radiotherapy, and chemotherapy, the aim of this study was to test the therapeutic potential of gene therapy for the treatment of glioblastoma multiforme (GBM). We have quantitatively analyzed two gene therapy approaches using short-term human glioma cell cultures derived from surgical biopsies (designated IN859, IN1612, IN2045, IN1760, and IN1265) and compared the results of gene therapy with the chemosensitivity of the same cells. All of the glioma cell cultures tested were susceptible to recombinant adenovirus (RAd)-mediated infection. Expression of herpes simplex virus type 1-thymidine kinase (RAd128), followed by ganciclovir treatment, induced apoptosis in all of the glioma cell cultures studied, including three that are resistant to the chemotherapeutic drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Expression of murine Fas ligand (RAdhCMV-mFasL) also induced cell death in four of the five cell cultures studied. One cell culture that was resistant to CCNU was also resistant to apoptosis induced by mFasL expression. These results suggest that sensitivity to chemotherapeutic agents does not necessarily correlate with the sensitivity to gene therapy treatments. RAds expressing therapeutic gene products in human glioma cell cultures are able to induce apoptosis even in some cells that are resistant to a commonly used chemotherapeutic agent. Therefore, RAd-mediated gene transfer could be a good candidate to further develop gene therapy for the treatment of GBM.

Adenoviridae↗
PubMed2006

A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with O6-methylguanine DNA methyltransferase.

Administration of chemotherapy is often limited by myelosuppression. Expression of drug-resistance genes in hematopoietic cells has been proposed as a means to decrease the toxicity of cytotoxic agents. In this pilot study, we utilized a retroviral vector expressing methylguanine DNA methyltransferase (MGMT) to transduce hematopoietic progenitors, which were subsequently used in the setting of alkylator therapy (procarbazine, CCNU, vincristine (PCV)) for poor prognosis brain tumors. Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells were collected by apheresis and enriched for CD34+ expression. Nine subjects were infused with CD34+-enriched cells treated in a transduction procedure involving a 4-day exposure to cytokines with vector exposure on days 3 and 4. No major adverse event was related to the gene therapy procedure. Importantly, the engraftment kinetics of the treated product was similar to unmanipulated peripheral blood stem cells, suggesting that the ex vivo manipulation did not significantly reduce engrafting progenitor cell function. Gene-transduced cells were detected in all subjects. Although the level and duration was limited, patients receiving cells transduced using fibronectin 'preloaded' with virus supernatant appeared to show improved in vivo marking frequency. These findings demonstrate the feasibility and safety of utilizing MGMT-transduced CD34+ peripheral blood progenitor cells in the setting of chemotherapy.

Adolescent↗
PubMed1997

Determining mutational fingerprints at the human p53 locus with a yeast functional assay: a new tool for molecular epidemiology.

In order to isolate experimentally induced p53 mutations, a yeast expression vector harbouring a human wild-type p53 cDNA was treated in vitro with the antineoplastic drug chloroethyl-cyclohexyl-nitroso-urea (CCNU) and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. p53 mutations were identified in 32 out of 39 plasmids rescued from independent ade- transformants. Ninety-two percent of CCNU induced mutations were GC-targeted single base pair substitutions, and GC > AT transitions represented 73% of all single base pair substitutions. In 70% of the cases the mutated G was preceded 5' by a purine. The distribution of the mutations along the p53 cDNA was not random: positions 734 and 785 appeared as CCNU mutational hotspots (n=3, P<0.0003) and CCNU induced only GC > AT transitions at those positions. The features of these CCNU-induced mutations are consistent with the hypothesis that O6-alkylguanine is the major causative lesion. One third of the CCNU-induced mutants were absent from a huge collection of 4496 p53 mutations in human tumours and cell lines, thus demonstrating that CCNU has a mutational spectrum which is uniquely different from that of naturally selected mutations. This strategy allows direct comparison of observed natural mutation spectra with experimentally induced mutation spectra and opens the way to a more rigorous approach in the field of molecular epidemiology.

Antineoplastic Agents, Alkylating↗
PubMed2001

Melanoma-associated retinopathy: does autoimmunity prolong survival?

PURPOSE: To discuss the autoimmune basis of melanoma-associated retinopathy (MAR) and its implications for management and prognosis. METHODS: An unusual history of a woman with melanoma-associated retinopathy is presented in detail. A review of published reports and a summary of 19 reported cases of MAR provide a basis for discussion. RESULTS: This case report and other published reports highlight a number of points regarding MAR including the male predominance, prolonged survival in several patients and lack of response to immunosuppression. CONCLUSIONS: Melanoma-associated retinopathy may prolong the survival of patients with metastatic melanoma through the autoimmune response. Therefore, treatment of visual symptoms with immunosuppression needs to be considered carefully.

Adult↗
PubMed2002

Coeliac disease following high-dose chemotherapy.

This report describes an interesting case of severe diarrhoea following high-dose chemotherapy for non-Hodgkin's lymphoma. This caused significant morbidity and resolved on a gluten-free diet.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Chemotherapy of low-grade gliomas.

Histologic subtypes of low-grade gliomas include pilocytic astrocytomas (World Health Organization [WHO] grade I), diffuse infiltrating astrocytomas, oligodendrogliomas, and mixed oligo-astrocytomas (WHO grade II). Although extended survival is typical with these tumors, most patients eventually succumb to recurrent or progressive disease despite receiving either adjuvant radiation therapy or radiation at the time of recurrence. Not surprisingly, chemotherapy for low-grade gliomas has primarily been evaluated in the salvage setting of postradiotherapy progression in both adults and children. Unfortunately, the published body of literature describing chemotherapy for these tumors is small and subject to a number of confounding methodologic limitations. Nonetheless, some guidelines for the use of chemotherapy in these patients can be inferred from the published experience. The data reviewed clearly identifies a potential benefit for PCV chemotherapy (procarbazine, CCNU, and vincristine) in at least a subset of patients with low-grade oligodendroglial tumors. Nitrosoureas and platinum agents appear to have modest efficacy in recurrent oligodendroglial tumors and in some patients with newly diagnosed or progressive low-grade astrocytomas; however, surgery and radiation remain the primary treatment modalities for this group of malignancies. Until new data becomes available, chemotherapy still should be used only as a salvage option in previously irradiated patients with recurrent or progressive low-grade gliomas.

Adolescent↗
PubMed2001

Multidisciplinary management of adult anaplastic oligodendrogliomas and anaplastic mixed oligo-astrocytomas.

Once thought to be rare, oligodendroglial tumors might actually represent up to 25% of primary glial neoplasms. In recent years, the histologic criteria for the diagnosis of oligodendroglioma have been broadened to include most small cell, monomorphic glial neoplasms. These refinements have led to an increased recognition of oligodendroglial neoplasms, but uniform definitions of pure versus mixed oligodendroglioma as well as the criteria for high-grade (anaplastic) versus low-grade tumors remain elusive. From a prognostic standpoint, the presence of an oligodendroglial component in a malignant glioma predicts longer survivals times for patients treated with surgery, and radiation therapy with or without chemotherapy. High rates of response to PCV (procarbazine, CCNU and Vincristine) chemotherapy also have been noted among patients with anaplastic oligodendroglial neoplasms. Ongoing prospective trials seek to clarify the role of PCV chemotherapy when added to radiation therapy and surgery. In addition, the role of molecular markers as diagnostic aides and guides to therapy and prognosis are being explored for patients with pure and mixed anaplastic oligodendroglial tumors.

Adult↗
PubMed1976

[Post-MOPP chemotherapy of Hodgkin's disease (author's transl)].

In 18 patients with advanced Hodgkin's disease, refractory to previous 'C-MOPP' treatment, a new therapeutic protocol of adriamycin, DTIC, CCNU and bleomycin was introduced. Three patients who had previously failed to respond to any other chemotherapy failed also to respond to the new one. But two complete and 11 partial remissions were obtained in the other 15 patients who had previously responded to C-MOPP before becoming refractory to it. Two patients had further progression of the disease during the new treatment.

Adult↗