Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Teniposide and etoposide are third-generation semi-synthetic derivatives of epipodophyllotoxin. Following the initial clinical introduction of teniposide in the 1970s, investigations focused almost exclusively on its analogue, etoposide, because of its formulation, which was felt to have advantages in addition to oral administration. Despite consistently inadequate dosing and scheduling, early phase I and II trial results with teniposide were promising, and current trends encourage a second look. The substantial antitumor activity of teniposide is comparable with that of etoposide, and clinical interest was rekindled when it was shown to have considerable activity against small cell lung cancer (SCLC). In view of the inadequacy of early trials and the premature cessation of clinical study, it is recommended that teniposide be reevaluated for its activity against malignant lymphomas, Hodgkin's disease, leukemias, and SCLC, against all of which its early results were encouraging. In addition, consideration should be given to its activity against brain tumors, neuroblastomas and other childhood solid tumors, and ovarian cancer; its potential value against gastric, hepatocellular, breast, and bladder cancers also should be investigated. Other areas that warrant further study include elucidation of the exact mechanism of action of teniposide, its role in both single- and multiple-agent chemotherapeutic regimens, and resolution of its optimal dose and schedule. Finally, it is suggested that with new routes of administration and improved formulations, teniposide may be expected to play a significant role in the treatment of malignant lymphomas, SCLC, and pediatric lymphocytic leukemia and neuroblastoma.
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PMID:Teniposide in adult solid tumors: a historical perspective. 141 38

With present techniques, hyperthermia used alone can cause complete clinical regression in 10-15% of tumours but the duration of response is very short. The greatest advantage for hyperthermia at the present time appears to be in combination with radiation in the local control of cancer growth. Currently, large randomised phase III studies are in progress to determine whether the addition of local hyperthermia to radiation or chemotherapy yields significant advantage. Phase III studies of wholebody hyperthermia in combination with chemotherapy are planned for the future and will include tumours with a high growth fraction such as small cell lung cancer and high grade non Hodgkins lymphoma.
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PMID:Hyperthermia in cancer growth regulation. 162 44

In patients with successfully treated Hodgkin's disease, lung cancers, and particularly small cell lung cancers, are not uncommon (relative risk: +/- 5) and result essentially from radiotherapy. What is usually considered as a late recurrence of small cell lung cancer occurs also frequently in long-term surviving patients after therapy for small cell lung cancer; it is hypothesized that at least some of these tumors might be in fact induced by the therapy used for the initial lung neoplasm.
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PMID:Secondary neoplasms following cancer treatment with a special emphasis on lung tumors. 164 73

Chemotherapy cures a minority of adult tumours (e.g. Hodgkin's and non-Hodgkin's lymphoma, acute leukaemia, teratoma) and the majority of childhood tumours. Prolongation of survival by chemotherapy has been shown for small cell lung cancer, ovarian cancer and breast carcinoma (when used as an adjuvant). However, in the majority of solid tumours there is a less than 20% response to chemotherapy and even curable tumours may relapse and become resistant. Resistance may be de novo, acquired as a stable change within the cell, or be rapidly inducible within the cell after drug administration. Several mechanisms have been described including multidrug resistance, glutathione transferases and DNA repair. Understanding these mechanisms may help to improve the therapeutic ratio and develop new approaches.
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PMID:Drug resistance. 165 Jun 21

Thymidine kinase (TK) is a biological marker recently used in diagnosis and monitoring of pulmonary and mediastinal malignant neoplasms. Authors report more recent clinical evidences of literature and, in the meanwhile, they report their personal experiences about a 20 patients group suffering of lung cancer and Hodgkin disease. Their study demonstrates a good sensitivity of TK as biological marker of SCLC and a lower sensitivity in case of NSCLC and Hodgkin disease. It has been possible to contribute to establishment of normal range values, on account of 10 healthy volunteer group blood sample assays.
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PMID:[Thymidine kinase as a biological marker in neoplasms of the lung and mediastinum]. 166 60

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

Etoposide is an important drug that has been recently incorporated with other agents in the curative treatment of patients with advanced neoplasms, including germ cell tumors, non-Hodgkin's lymphomas (NHL), and small cell lung cancer (SCLC). Etoposide demonstrates remarkable schedule dependency. A randomized comparison has shown an impressive survival difference for patients with extensive SCLC receiving a 5-day course versus those receiving a 1-day course. Because of these and previous clinical and laboratory data, etoposide is now given intravenously or orally in a 3-day to 5-day schedule. It is generally accepted that approximately 50% of the orally administered drug is absorbed. The authors have initiated several etoposide studies using an extended administration schedule, believing that a prolonged schedule may be superior to the standard 3-day to 5-day schedule. This was initially tested in a Phase I study. Results showed that etoposide (50 mg/m2/d) given over 21 days was feasible and was associated with only moderate toxicity. Several Phase II studies have been completed or are nearing completion, including studies in patients with SCLC, NHL, germ cell tumors, soft tissue sarcoma, renal carcinoma, and ovarian carcinoma. Responses have been seen in all of these groups, particularly in patients with SCLC, lymphoma, and germ cell tumors. In these groups we saw responses in patients who were clearly resistant to etoposide plus cisplatin given in a standard schedule or in some patients who were resistant to high-dose etoposide with bone marrow transplantation. Investigators at Indiana University Medical Center who studied oral etoposide in a similar fashion in patients with advanced germ cell tumors and SCLC achieved results similar to those reported here. The authors have initiated a number of combination chemotherapy programs using the chronic oral form of etoposide. These include patients with SCLC, non-small cell lung cancer, and elderly patients with high-grade and intermediate forms of NHL. In addition, chronic intravenous oral etoposide is being used in salvage approaches for patients with acute myelocytic leukemia and recurrent resistant intermediate-grade and high-grade NHL. Preliminary pharmacokinetic data suggest that a 50-mg/m2 oral dose is highly bioavailable (91% to 96%). Therefore, during a prolonged oral course at 50 mg/m2, many patients maintain a minimum plasma concentration of 1 microgram/ml. Further studies of multiple dose or continuous infusion etoposide to maintain a potentially critical plasma level are in progress. Etoposide administered in this way could represent a "new" drug because many of its features are different, and its activity spectrum may be broader.
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PMID:Chronic oral etoposide. 198 32

Chemotherapy is the main treatment in many human malignancies including non-Hodgkin lymphomas and some solid tumors such as those of embryonal origin and small cell lung carcinomas. The high responsiveness to chemotherapy of these tumors has led some groups to treatment policies limited to chemotherapy alone. A long follow-up has shown a high incidence of recurrence in the sites that were initially macroscopically involved. Some randomized trials evaluating the adjunction of radiotherapy to chemotherapy have shown that a failure in local control can be associated with a decreased overall survival. The survival benefit of combined chemotherapy and radiotherapy is generally moderate and is best evaluated by randomized trials entering a large number of patients. The adjunction of radiotherapy to chemotherapy can lead to an increased rate of acute and late toxicity that may overshadow a therapeutic benefit. Critical points of the combined approach are: types of drugs, radiotherapy parameters, radiotherapy-chemotherapy doses, and timing. In this review, two clinical models, one with a low potential of cure, limited small cell lung cancer, and one with a medium potential of cure, non-Hodgkin lymphoma, are reviewed emphasizing information obtained from randomized trials. The modalities of combining radiotherapy and chemotherapy, particularly the timing, are analyzed to define optimal schedules for a definite therapeutic gain.
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PMID:The value of adjunctive radiotherapy when chemotherapy is the major curative method. 217 41

A nation-wide clinical trial on a new antineoplastic drug, carboplatin(CP) supplied by Qilu Pharmaceutical Company, was carried out during the period of January to September 1989. Two hundred and forty-three patients with various malignant tumors were treated by CP as a single agent, 167-436 mg/m2 by intravenous infusion, repeated every 4 weeks, and 2-4 cycles as a course. The response rate was 75% (6/8) in testicular cancer, 56% (9/16) in ovarian cancer, 63% (15/24) in head and neck cancer, 37% (15/41) in small cell lung cancer and 60% (25/42) in non-Hodgkin's lymphomas. Randomized study of combination chemotherapy containing CP or cisplatin (DDP) was also conducted. The results showed that in small cell lung cancer, 73% (30/41) of the the patients responded to CE (CP + VP - 16) and 67% (24/36) responded to PE (DDP + VP - 16) and in ovarian cancer, the response rate was 60% (6/10) to CAC (CP + adriamycin + cyclophosphamide) and 36% (4/11) to PAC (DDP + adriamycin + cyclophosphamide) regimen. In addition, gastrointestinal reaction and renal toxicity were less severe in regimens containing CP than in regimens containing DDP. However, CP had more marked myelosuppressive effect.
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PMID:[Clinical results of carboplatin in the treatment of malignant tumors. Clinical Cooperative Group of Carboplatin]. 217 94

Cancer chemotherapy provides variably effective treatment for the majority of forms of human cancer and curative treatment for some 12 categories of cancer. Curative treatment is defined as the proportion of patients who survive beyond the time after which the risk of treatment failure approaches zero, i.e., the disease-free survival plateau. This progress has resulted from a closely integrated scientific effort, including drug development, pharmacology, preclinical modeling, experimental design with respect to clinical trials, quantitative criteria for response, and a series of clinical trials (initially in children with acute lymphocytic leukemia) in which the importance of complete remission, of dose and schedule, of sequencing chemotherapeutic agents, of pharmacological sanctuaries, and particularly of combination chemotherapy was studied. The principles derived from these studies, particularly those relating to combination chemotherapy, resulted in curative treatment for disseminated Hodgkin's disease, non-Hodgkin's lymphoma, pediatric solid tumors, testicular cancer, and limited small cell lung cancer. Many patients with certain stages of solid tumors, such as breast cancer and osteogenic sarcoma, are at high risk of having disseminated microscopic disease. Experimental studies indicate that treatment which is only partially effective against macroscopic disease is much more effective against microscopic tumors. Therefore chemotherapy is administered immediately following control of the primary tumor in patients at high risk of having disseminated microscopic disease, a treatment known as adjuvant chemotherapy. This program has been highly successful in increasing the cure rate in patients with pediatric solid tumors and in prolonging disease-free survival in patients with premenopausal breast cancer. Given dissemination of the technology, it is estimated that 15,000-30,000 patients per year are potentially curable in the United States. Curability of cancer by chemotherapy generally is inversely related to age, i.e., the above tumors are most common in children and young adults. There are new and promising treatment strategies, such as neoadjuvant chemotherapy and autologous bone marrow transplantation. The revolution in molecular and cellular biology is providing an increase in targets, rationale, and opportunity for more effective and novel chemotherapeutic approaches.
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PMID:Curative cancer chemotherapy. 299 3


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