-
Journal of the National Medical... Oct 1985An update in cancer chemotherapy that deals with the various therapies of lung cancer is described. At present, the stage of the disease and cell type are the major... (Review)
Review
An update in cancer chemotherapy that deals with the various therapies of lung cancer is described. At present, the stage of the disease and cell type are the major factors that determine the treatment. Important differences in the biological behavior and response to treatment exist between small cell and non-small cell cancers. The small cell type is sensitive to many chemotherapeutic agents. Differences in response to chemotherapy and survival have been less among the non-small cell types.The treatment of non-small cell carcinomas including squamous cell, large cell, and adenocarcinoma are reviewed in Part I of this paper. Small cell lung cancer will be described in Part II, which will be published in a future issue of the journal.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Bleomycin; Carcinoma; Carcinoma, Squamous Cell; Cyclophosphamide; Dactinomycin; Doxorubicin; Fluorouracil; Humans; Lomustine; Lung Neoplasms; Mechlorethamine; Methotrexate; Mitomycin; Mitomycins; Neoplasm Staging; Peptichemio; Prednisone; Procarbazine; Prognosis; Vincristine
PubMed: 2414458
DOI: No ID Found -
British Journal of Cancer May 1996The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish patients with different prognoses. This paper explores the possibility of improving the prognostic forecast in MM by considering some clinical characteristics at diagnosis together with response to first-line chemotherapy. A total of 231 patients were prospectively randomised in a multicentre trial to no therapy vs melphalan + prednisone (MP) for stage I, MP in stage II, and MP vs peptichemio, vincristine and prednisone for stage III. The clinical features of these groups were evaluated for prognostic variables predictive of overall survival by means of univariate and multivariate analysis. The independently significant variables were incorporated into a model that identified three groups of patients with different risks of death and different overall survival. Three variables retained statistical significance: the staging system proposed by the British Medical Research Council, a composite parameter integrating the percentage of bone marrow plasma cells with cytological features of the infiltrating elements (plasma cell vs plasmablast), and response to 6 months of first-line chemotherapy. These three variables led the proposal of a scoring system able to identify three different risk classes (with median overall survival of 52, 28 and 13 months respectively) and to estimate individual patient prognosis more flexibly. The proposed risk classes, drawn from both diagnostic and therapeutic parameters, are thought to be a clinical and investigational instrument for separating MM patients into comparable groups, for selecting the best available therapy and for evaluating response with respect to the disease of each new patient.
Topics: Aged; Antineoplastic Agents; Bone Marrow; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunoglobulin Isotypes; Male; Melphalan; Multiple Myeloma; Multivariate Analysis; Neoplasm Staging; Peptichemio; Plasma Cells; Prednisone; Probability; Prognosis; Prospective Studies; Risk Assessment; Survival Rate; Time Factors; Vincristine
PubMed: 8624271
DOI: 10.1038/bjc.1996.212 -
British Journal of Cancer Dec 1994The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma.
The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases.
Topics: Antineoplastic Agents; Creatinine; Female; Humans; Male; Multiple Myeloma; Prospective Studies; Survival Analysis; Time Factors
PubMed: 7981078
DOI: 10.1038/bjc.1994.474 -
Hinyokika Kiyo. Acta Urologica Japonica Nov 1987A rare case of prostatic rhabdomyosarcoma in a 3-year-old child is presented. He received a multimodal treatment of chemotherapy including vincristine, cyclophosphamide,... (Review)
Review
A rare case of prostatic rhabdomyosarcoma in a 3-year-old child is presented. He received a multimodal treatment of chemotherapy including vincristine, cyclophosphamide, actinomycin-D plus adriamycin, and linac irradiation followed by total prostatectomy with segmental resection of bladder. Despite no viable sarcoma cells in the surgical specimen, he showed relapse 4 months later. By the combination of cisplatin, vinblastine and peplomycin (PVP therapy), the bulky mass in the pelvis rapidly reduced by 95%. Furthermore, cisplatin, etoposide and peplomycin (PEP therapy), instead of PVP therapy, were administered to the refractory disease. Although the residual tumor was salvaged after 7 courses of PEP therapy, abdominal dissemination and liver metastasis occurred 2 months postoperatively. The combined modality of vincristine, peplomycin, ifosfamide, methotrexate, adriamycin, melphalan plus nimustine, and irradiation of microtron were effective for the abdominal dissemination, but he died of cerebral hemorrhage 31 months after the start of treatment. We emphasize that more aggressive chemotherapy including cisplatin, etoposide and so on is required to manage the advanced, relapsed, or resistant cases compared to the usual modality of rhabdomyosarcoma.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Dactinomycin; Etoposide; Humans; Male; Neoplasm Recurrence, Local; Peplomycin; Peptichemio; Prednisone; Prostatic Neoplasms; Rhabdomyosarcoma; Vincristine
PubMed: 2451411
DOI: No ID Found -
British Journal of Cancer Sep 1988A 15 month old boy with a stage IV right suprarenal gland neuroblastoma showed a number of raised biochemical parameters, whilst catecholamines and skeletal survey were...
A 15 month old boy with a stage IV right suprarenal gland neuroblastoma showed a number of raised biochemical parameters, whilst catecholamines and skeletal survey were normal. Treatment with peptichemio failed to give a clinical response. Histological evidence of neuroblastoma infiltration in the bone marrow aspirate was absent. Immunofluorescence on sedimented cells was negative using antibody UJ223.8, PI153/3 and H11; only UJ308 and to a lesser extent UJ13A gave positive results. After 21 days, however, the same cells in culture showed highly differentiated dendritic processes. Thirty-seven percent metaphases from bone marrow aspirate showed the following karyotype 45XY, del (1) (p32), and two markers. Mar1 = der (2) t (2; 2) (2qter----2q14::2p24----2qter). Mar2 = der (15) t (15; 2) (15qter----15p11::2p11----2pter). Treatment with methotrexate reduced the aberrant mitoses rate to 2%. N-myc in situ hybridisation showed significant signal on both markers confirming the cytogenetic interpretation. Peripheral blood lymphocytes at 72 h showed a higher level of breaks per cell than control. After treatment with aphidicolin (APC) or methotrexate (MTX) for the last 24 h, to induce fragile sites, the incidence of breaks per cells was increased. Moreover 11.4% of APC-induced breaks were in 1p31-32 (mean of normal controls = 2.3%). The mother presented an increased sensitivity to the inducibility of fragile sites, while the father's lymphocytes showed values within the control range. The genetic changes produced by the abnormalities on chromosomes 1 and 2 might be related to tumour progression. Furthermore this is the first description of correlation between a high frequency of fragile site 1p31-32 induced by APC in the patient's lymphocytes and deletion of 1p32 in tumour cells. The interpretation of these findings and of other similar correlations needs further study.
Topics: Adrenal Gland Neoplasms; Bone Marrow; Chromosome Aberrations; Chromosome Disorders; Chromosome Fragile Sites; Chromosome Fragility; Humans; Infant; Karyotyping; Male; Neuroblastoma; Nucleic Acid Hybridization; Oncogenes
PubMed: 3179179
DOI: 10.1038/bjc.1988.205 -
British Journal of Cancer Aug 1998m-L-sarcolysin (m-L-SL) is an isomer of melphalan (Mel) with the di(2-chloroethyl) amino group being substituted in the meta position of phenylalanine. By covalent... (Comparative Study)
Comparative Study
Comparison of the cytotoxic activity of melphalan with L-prolyl-m-L-sarcolysyl-L-p-fluorophenylalanine in human tumour cell lines and primary cultures of tumour cells from patients.
m-L-sarcolysin (m-L-SL) is an isomer of melphalan (Mel) with the di(2-chloroethyl) amino group being substituted in the meta position of phenylalanine. By covalent conjugation of amino acids to m-L-SL, a peptide complex consisting of six m-L-SL-based oligopeptides known as peptichemio (PTC) was developed previously. In the present study, the cytotoxic activity pattern of the different oligopeptides of PTC was investigated in ten human tumour cell lines representing different mechanisms of cytotoxic drug resistance using the fluorometric microculture cytotoxicity assay (FMCA). In the cell line panel, L-prolyl-m-L-sarcolysyl-L-p-fluorophenylalanine (P2) was the most active oligopeptide, showing slightly lower mean IC50 values (2.6 vs 3.9 and 4.1 microg ml(-1)) than Mel and m-L-SL. The other five oligopeptides were less active than Mel. All active oligopeptides showed mechanistic similarity to Mel as judged by the correlation analysis of the cell line panel log IC50 values (R > or = 0.90), although P2 appeared to be less sensitive to GSH-mediated drug resistance. The relative activity of Mel and P2 was found to be related to degree of proliferation, P2 being more active towards low-proliferating cell lines. P2 and Mel were then further characterized in 49 fresh human tumour samples. In these samples P2 was considerably more active than Mel and showed a higher relative solid tumour activity (2.7 to 4.5-fold). However, the correlation of log IC50s between P2 and Mel in patient cells was high (R = 0.79), indicating a similar mechanism of action in this tumour model too. Cross-resistance with other standard drugs was lower for P2 than Mel. The results show that P2 is the most potent component of PTC and demonstrates a favourable activity profile compared with Mel. These data suggest that further investigation of P2 as a potential anti-tumour agent is warranted.
Topics: Cell Line; Drug Resistance, Neoplasm; Humans; Melphalan; Oligopeptides; Peptichemio; Tumor Cells, Cultured
PubMed: 9703278
DOI: 10.1038/bjc.1998.494 -
British Journal of Cancer Apr 1993The effects of a combination chemotherapy (CAV-PVP) consisting of cyclophosphamide, doxorubicin, hydrochloride (dox) and vincristine (CAV) alternating with cisplatin and... (Clinical Trial)
Clinical Trial
Effect of alternating combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide for small cell lung cancer on hematopoietic progenitors in the peripheral blood.
The effects of a combination chemotherapy (CAV-PVP) consisting of cyclophosphamide, doxorubicin, hydrochloride (dox) and vincristine (CAV) alternating with cisplatin and etoposide (PVP) on peripheral blood hematopoietic progenitor cells (PBHPs) were studied in five patients with small cell lung cancer (SCLC). The kinetics of the CFU-GM levels were different during the CAV and PVP phases. None of the five patients displayed a rebound increase in the level of peripheral blood CFU-GM during the CAV phase. In contrast, all five patients displayed a rebound increase in peripheral blood CFU-GM levels during the PVP phase of the alternative combination chemotherapy (3-5 weeks after the initiation of PVP regimen). These findings indicate the optimal timing for leukapheresis to obtain PBHPs in SCLC patients which have been treated with an alternating combination chemotherapy consisting of CAV-PVP.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Hematopoietic Stem Cells; Humans; Leukocytes, Mononuclear; Lung Neoplasms; Macrophages; Male; Middle Aged; Peptichemio; Prednisone; Stimulation, Chemical; Vincristine
PubMed: 8385979
DOI: 10.1038/bjc.1993.145 -
Hinyokika Kiyo. Acta Urologica Japonica Apr 1986A retrospective study was conducted on 22 patients with renal pelvic tumor treated at our University Hospital between 1970 and 1984. The patients included 18 males and 4...
A retrospective study was conducted on 22 patients with renal pelvic tumor treated at our University Hospital between 1970 and 1984. The patients included 18 males and 4 females, from 31 to 81 years of age. The left kidney was involved in 14 cases, and the right in 8. More than 60% of them also presented gross hematuria. IVP abnormalities included filling defects in 9 cases and non-visualizing kidney in 8 cases. Pretreatment urinary cytology was positive in 65.7%. Radical nephroureterectomy was performed in 18 cases, followed by adjuvant therapy in 10 cases; radiation in 5 cases, chemotherapy in 4 cases, and radiation/chemotherapy in one case. Histology revealed transitional cell carcinoma in all cases. On diagnosis, simultaneous urothelial tumors were identified in one case in the ureter and the bladder, and in one case in the bladder. Tumor development after surgery was observed in 9 cases, 8 in the bladder and one in the ipsilateral renal pelvis. The 5-year actual survival rate was 58.2% over all: that of the low-grade group was 100%; that of the high-grade group, 45.1%; that of the low-stage group, 100%; that of the high-stage group, 19%. In conclusion, the prognosis in our series was significantly influenced by the stage and grade of the tumor.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Kidney Neoplasms; Kidney Pelvis; Male; Middle Aged; Peptichemio; Prognosis; Retrospective Studies
PubMed: 3755565
DOI: No ID Found -
British Journal of Cancer Mar 1996In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and epirubicin (70 mg m-2), administered every 3 weeks for three courses and both associated with prednisone and interferon-alpha2b. Both regimens were administered on an outpatient basis and had low haematological toxicity. Clinical results were similar. Overall response rate (43%) and median response and survival (5.9 and 14.1 months respectively) compare well with those obtained with more aggressive chemotherapy schedules.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Drug Administration Schedule; Epirubicin; Female; Humans; Interferon alpha-2; Interferon-alpha; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloproliferative Disorders; Peptichemio; Prednisone; Recombinant Proteins; Vincristine
PubMed: 8611382
DOI: 10.1038/bjc.1996.138 -
Acta Haematologica 1980
Topics: Drug Therapy, Combination; Humans; Multiple Myeloma; Peptichemio; Vincristine
PubMed: 6778051
DOI: 10.1159/000207239