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PubMedDate not supplied

Alternating combination chemotherapy does not delay development of refractoriness in myeloma.

Sixty-seven patients with stage II and III myeloma were subjected to 3 consecutive prospective phase II studies. Nineteen patients had received melphalan - prednisolone (melphalan group), 17 cyclophosphamide - vincristine - prednisolone (cyclophosphamide group) and 22 alternating combinations of 7 cytostatics and prednisolone (alternating group). Nine patients were unevaluable. The median time until response was achieved was 5, 5 and 3 months respectively. The purpose of the study was to see if combination or alternating combination chemotherapy can delay the appearance of refractoriness. Patients were regarded as refractory after progression, which was defined as advance from stage II to stage III, and, in stage III as an increase of the monoclonal serum protein of more than 25% and/or the monoclonal urine protein of more than 100% despite continued treatment. Refractoriness was not delayed by alternating combination treatment. Thirty per cent of the patients became refractory after 10 months of response in the melphalan group and after 11 months in the cyclophosphamide and the alternating chemotherapy groups. The results remained after stratification for stage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

[Results of a pilot study of hyaluronidase as an adjunct to cytostatic therapy in malignant diseases].

46 patients (17 myelomas, 11 malignant lymphomas, 8 mammary carcinomas, 7 head and neck carcinomas, 2 gastrointestinal carcinomas and 1 ovarian carcinoma) were treated with Permease prepared of bovine testes by Sanabo. 7500 i.u. were given either intramuscular one hour before cytostatic chemotherapy or intraperitoneally with cytostatic agents. There were 2 cases of local irritation on the site of injection and 1 case of reversible anaphylactoid reaction. Results achieved in patients treated with the same chemotherapy in spite of resistance, but with addition of Permease: myeloma CR 2/9, subjective improvement 7/9; 5 patients expired, median observation time: 13 months; non-Hodgkin-lymphomas CR 2/5, PR 2/5; 2 patients expired, median observation time: 9 months; breast cancer PR 2/4, 2 patients expired, median observation time: 5 months, 1 patient with Morbus Hodgkin CR, expired after 24 months. The other patients who received systemic treatment had either primary chemotherapy with addition of Permease, or chemotherapy was altered because of resistance against the prior therapy before Permease was applied. Intraperitoneal application of Permease together with cytostatic agents, usually not used for local therapy because of high rate of irritation like cis-platin, was well tolerated. Complete regression of ascites was achieved in all cases. In 1 of the 4 patients duration of remission was 7 months. Hypotheses concerning the mechanism of action of hyaluronidase in malignant diseases are discussed. The effectiveness of Permease might be related to resistance phenomenon of tumor cells or to alteration of pharmacokinetics of cytostatic agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Aggressive combination chemotherapy in multiple myeloma. A multicentre trial. Finnish Leukaemia Group.

A one-armed multicentre trial was conducted in Finland during the period from Jan. 1979 to Feb. 1980 to document the possible beneficial effect of aggressive combination chemotherapy MOCCA on the remission induction and survival in multiple myeloma. The regimen MOCCA consisted of vincristine, methylprednisolone and 3 alkylating agents. Of the 50 patients eligible for the for study, 39 (78%) achieved at least a 50% response. 27 (54%) achieved an excellent response. The median survival time for all patients was 49 months from the initiation of the treatment, but 23 of the 33 patients whose myeloma protein had shown a greater than or equal to or greater than or equal to 75% reduction were still alive at 4 yr. Advanced clinical stage and irreversible renal damage had a negative prognostic value. After 12 months on regimen MOCCA the patients with a greater than or equal to or greater than or equal to 75% reduction in myeloma protein were allocated at random to receive MOCCA courses bimonthly or no further chemotherapy. The maintenance chemotherapy did not prolong remission or survival.

Adult↗
PubMedDate not supplied

Chemotherapy plus immunotherapy for patients with primary and metastatic brain tumors.

The authors report two clinical trials concerning chemotherapy and immunotherapy combined in the treatment of primary and metastatic brain tumors. In the first study bacillus Calmette-Guerin (BCG) and in the second Levamisole (LMS) were utilized as immunostimulating agents. Chemotherapy was performed with BCNU or CCNU in association with surgery and/or radiotherapy. The immunological response was obtained but immunotherapy failed to demonstrate any significant effect on survival.

Astrocytoma↗
PubMed1986

Increased therapeutic benefit through the addition of misonidazole to a nitrosourea-radiation combination.

The potential therapeutic advantage of including the radiosensitizer misonidazole (MISO) in a treatment regimen combining systemic chemotherapy and localized radiotherapy was assessed in the KHT sarcoma. Tumor-bearing C3H mice were treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, administered either alone or in combination with MISO, 24 h prior to irradiating the tumors with doses ranging from 0-35 Gy. The sensitizer exposure was either a single dose of 2.5 mmol/kg or multiple injections given every 0.5 h for 8 h to maintain a sensitizer blood level of approximately 100 micrograms/ml. The chemotherapeutic agent was administered simultaneously with the single sensitizer dose or 3 h into the chronic sensitizer dosing schedule. Tumor responses to the combined modality treatments was determined using end points of tumor regrowth delay and animal tumor-free survival. Skin reactions in the treatment field were scored as a measure of normal tissue complications. MISO, administered as a single dose in the combined modality therapy, enhanced the tumor response by a factor of approximately 1.8-1.9 while increasing skin reactions approximately 1.1- to 1.2-fold. Combining 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea with chronic MISO administration prior to irradiation increased the resultant tumor control probability 1.5- to 1.8-fold without enhancing normal tissue complications. Consequently using MISO as a chemopotentiator in a 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-radiation combination can yield a significant therapeutic benefit.

Animals↗
PubMed1985

In vivo interaction between radiation and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in the absence or presence of misonidazole in mice.

The effect of combining the radiosensitizer misonidazole (MISO) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) prior to radiation on the response of various KHT sarcoma cell subpopulations was evaluated. Centrifugal elutriation was used to obtain homogeneous populations of cells with respect to their cell cycle position from suspensions prepared directly from treated solid KHT tumors. Survival in these subpopulations was determined using an in vivo to in vitro cloning assay. In situ treatment consisted of either (a) CCNU (3.0 mg/kg) plus MISO (1.0 mg/g), (b) radiation (15 Gy) alone, or (c) CCNU plus MISO preceding the radiation by 24 hr. In the latter protocol, one treatment effectively eliminated those cells being preferentially spared by the other. The CCNU-MISO followed by radiation combination not only reduced the treatment resistance due to hypoxia and cell cycle position but also left all cell subpopulations in the tumor equally sensitive to the treatment. To determine the nature of the interaction between these agents in detail, the extent of cell killing following such a treatment regimen was evaluated using isoeffect plot (isobologram) analysis. KHT sarcoma-bearing C3H mice were treated with various doses of CCNU either alone or in simultaneous combination with a 1.0-mg/g dose of MISO 24 hr prior to receiving a range of radiation doses. Combining CCNU and radiation led to significantly enhanced tumor cell killing. When evaluated by isoeffect plot analysis, the data points resulting from this combination fell well below the envelope of additivity, indicating that a supraadditive interaction between these two agents had occurred in the tumor cells. An even greater interaction was observed in the KHT sarcomas when MISO was combined with CCNU prior to irradiation. The findings of effective elimination of treatment-resistant subpopulations along with a supraadditive tumor cell kill offer, at least in part, an explanation for the previously described therapeutic advantage observed for the CCNU-MISO-radiation protocol.

Animals↗
PubMed1985

[Inoperable lung epidermoid cancer non metastasizing. A phase II trial using radiotherapy and combined chemotherapy].

Thirty three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a Phase II study combining chemotherapy (Vindesine 1.5 mg/m2 dl; CCNU 50 mg/m2 d2, 25 mg/m2 d3; Cis-Platinum 100 mg/m2 d3; Cyclophosphamide 200 mg/m2 d3, 4, 5) (VCPC) and radical radiotherapy to the primary tumor, mediastinum and supraclavicular nodes. Responders to chemotherapy resumed four additional cycles following radiation therapy. Fourteen patients (42%) presented an objective response to the first two cycles of VCPC. On final evaluation, 18 patients (54.5%) obtained a complete remission and 6 patients (18%) a partial remission. Median survival of all patients was 15.9 months and toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.

Adult↗
PubMed1985

The influence of the antimitotic drug CCNU on the neurosecretion of rat hypothalamo-hypophyseal system.

The purpose of this investigation was to evaluate the influence of the antimitotic drug CCNU on the morphology of the hypothalamo-hypophyseal neurosecretory system of rat. Adult Wistar rats were treated intragastrically with 2.5 mg CCNU once a week during 3 consecutive weeks and 5 mg at the end of the 4th week. The brains and hypophyses were fixed in Zenker-formol solution. Paraffin slices were stained with chromhematoxylin to demonstrate neurosecretory material and with cresyl violet. PAS reaction was also performed. The experiment resulted in disturbances of the neurosecretory function of the hypothalamo-hypophyseal system in form of alteration in the content of neurosecretion in the neuronal cytoplasm and processes within supraoptic and paraventricular nuclei as well as in the neurohypophysis. The morphometric measurements showed enlargement of the cell nuclei and cytoplasm volumes in the nucleus supraopticus of hypothalamus.

Animals↗
PubMed1985

[Combination vindesine, cyclophosphamide, cis-platinum and CCNU in esophageal epidermoid cancer. Preliminary analysis of 64 cases].

We have treated 64 patients with esophageal squamous cell carcinoma using a combination of Vindesine 1.4 mg/m2 on day 1-2, Cyclophosphamide 200 mg/m2 on day 2-3-4, Cis-Platin 100 mg/m2 on day 3 and CCNU. 28 of the 37 patients considered to be inoperable were evaluable. We observed three complete responses and three partial responses in this group (overall response rate 21,5%). Twenty seven patients considered to be operable received the same chemotherapy without CCNU, owing to the risk of thrombopenia. 23 of these patients were evaluable in whom we observed 35% partial responses and no complete responses. No severe toxicity related to the chemotherapy protocol was observed. The mediocre results among the group of inoperable patients suggest that other chemotherapy protocols need to be tested. On the other hand, in the group of operable patients, the preliminary results encourage us to continue this study.

Adult↗
PubMed1985

[Brain tumors in infants and children--factors affecting prognosis, (Part-3). Mode of metastasis and prognosis in medulloblastoma].

Brain tumors in infants and children are different from those in adults in type and location of tumor as well as accompanying complication. Given this fact, and the fact that these patients are under development, careful consideration is required for determination of treatment planning. Thus, we have investigated the curative results of brain tumors in infants and children and factors effecting prognosis. In this study, medulloblastoma which is one of the most malignant pediatric brain tumors was analyzed in 64 cases in light of mode of metastasis and prognosis. Among those cases, there were 23 cases which were diagnosed to have metastasis or infiltration of tumor from the original site of the fourth ventricle. As mode of the cerebrospinal fluid circulation, 6 intracerebral solitary metastasis, 1 entraspinal cord metastasis, 1 intraperitoneal metastasis via shunt and 7 generalized metastases involving bone in 5, lymphnodes in 2 and liver, spleen, kidney, lung and peintoneal cavity in 1 respectively. The survival rate in those 23 cases with tumor metastasis or infiltration was 63.6% in one year, 28.6% in two years and 11.8% in five years and the average survival year was 8.1 months in cases who died of these tumor metastasis. Six of them had tumor metastasis with in 6 months after the initial treatment(s). There was no significant correlations in rate or occurrence of tumor metastasis between group of total resection and of partial resection nor group of whole neuro-axis radiation and of local radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗