Direct conversion from tramadol to tapentadol prolonged release for moderate to severe, chronic malignant tumour-related pain.

BACKGROUND: A recent randomized-withdrawal, active- and placebo-controlled, double-blind phase 3 study showed that tapentadol prolonged release (PR) was effective and well tolerated for managing moderate to severe, chronic malignant tumour-related pain in patients who were opioid naive or dissatisfied with current treatment (Pain Physician, 2014, 17, 329-343). This post hoc, subgroup analysis evaluated the efficacy and tolerability of tapentadol PR in patients who previously received and were dissatisfied with tramadol for any reason and who had a pain intensity ≥5 (11-point numerical rating scale) before converting directly to tapentadol PR. METHODS: In the original study, eligible patients had been randomized (2:1) and titrated to their optimal dose of tapentadol PR (100-250 mg bid) or morphine sulphate-controlled release (40-100 mg bid) over 2 weeks. The present report focuses on results during the titration period for a subgroup of patients randomized to tapentadol PR after having been on tramadol treatment prior to randomization in the study (n = 129). Results for this subgroup are compared with results for all 338 patients who received tapentadol PR during titration (overall tapentadol PR group). RESULTS: Responder rates (responders: completed titration, mean pain intensity <5 [0-10 scale] and ≤20 mg/day rescue medication during last 3 days) were slightly better for the tramadol/tapentadol PR subgroup (69.8% [90/129]) vs. the overall tapentadol PR group (63.9% [214/335]). Tolerability profiles were comparable for both groups. CONCLUSIONS: Results of this subgroup analysis indicate that patients with cancer pain could safely switch from prior treatment with the weak centrally acting analgesic tramadol directly to the strong centrally acting analgesic tapentadol PR, for an improved analgesic therapy for severe pain. WHAT DOES THIS STUDY ADD?: Results of this post hoc analysis show that patients who had received prior tramadol therapy could switch directly to tapentadol PR, with the majority (˜70%) experiencing improved efficacy.

A new spacing material for interstitial implantation of radioactive seeds.

Poly-p-dioxanon sutures (PDS) have been common in surgery as an absorbable material for years. After hardening by a particular procedure we use PDS pins as spacer material in interstitial I-125 implantations. The advantages of PDS are the mechanical qualities in contrast to catgut which causes hazards because of its soft consistency. PDS supports the efforts in optimization of seed distribution and dose application in interstitial radiotherapy.

Misonidazole and irradiation in the treatment of high-grade astrocytomas: further report of the Vienna Study Group.

A randomized study investigating the value of misonidazole in patients irradiated for grade III and IV supratentorial astrocytomas was started in June 1977. With a minimum follow-up time of 6 months, 45 patients who completed therapy are available for analysis. All patients received the same radiation treatment (66.5 Gy in 31 fractions over 7.5 weeks, field size reduction after 45 Gy). In the first, second and eighth week, a 4 Gy tumor dose was given on Monday and Thursday. Misonidazole was given 4 hours before irradiation to 18 randomized patients on those 6 treatment days (2.1-2.7 g/m2 per treatment day). Daily tumor doses of 1.7 Gy were administered Monday through Friday from the third until the seventh week. Median survival for patients treated with misonidazole is 13.8 months; for those treated by irradiation alone it was 9.8 months. The corresponding 1 year survival rates are 64 and 25%, respectively. Survival plots indicate some advantage for the patients treated with misonidazole, however statistically there is no significant difference observed (p greater than 0.08). There are no significant differences in Karnofsky performance status, sex and in histological grade or in age distribution between the groups. However, the type of surgery (complete or subtotal) influenced survival markedly: patients with complete surgery lived significantly longer (p less than 0.0009). Neurotoxic side effects of misonidazole were minimal.

Electron beam therapy in treatment of parotid neoplasm.

In a retrospective analysis, 42 patients with malignant primary tumor of the parotid gland were evaluated considering survival, local recurrence and tolerance of treatment. All patients referred to radiotherapy were treated by electron beam (10-15 MeV) and followed for more than 5 years. Postoperative radiotherapy after radical operation, with no macroscopic disease, was performed in 18 patients, 7 of whom were treated by radical re-operation and radiation of a recurrent parotid neoplasm. In these groups, the local recurrence rate was 4/18 (22%) and 2/7 (29%), the 5-year survival rate was 9/18 (50%) and 5/7 (71%). In 17 patients, radiotherapy started with gross tumor left behind. This group showed a local recurrence rate of 10/17 (59%) and a 5-year survival of 7/17 (41%). Treatment was well tolerated with no major sequelae. Local tumor control and its impact on survival is discussed.

Radiooncological management of very advanced extragonadal seminomas.

Five case histories involving extragonadal type-I Dixon-Moore seminomas are described, each having a large retroperitoneal tumor growth with, variously, lymph node or lung metastases, growth into or around organs, blood vessels and muscles, etc. The large tumor masses could be completely resected in some cases only. In three cases, post-operative combined radio- and chemotherapy have left the patients tumor-free for several years; in two cases radiotherapy given along resulted in a full remission. In one case, the undescended testis, in another, the fibrous tissue in an atrophic testicle of a patient evincing Turner's syndrome were shown not to contain primary tumor. The excellent therapeutic results confirm the correctness of the combined surgical, radiotherapeutic and chemotherapeutic treatment; it appears that correct timing of the various therapies is of prime importance.

[The value and limitation of echotomography in the diagnosis of abdominal lymphomas in malignant diseases(author's transl)]. / Die Wertigkeit und Grenzen der Echographie für die Diagnostik abdomineller Lymphome bei malignen Erkrankungen

The indication for ultrasonic examination in addition to endolymphatic methods is discussed. In 23 histologically proved advanced cases the accuracy of lymphography was 77% and in echotomography 74%. In the diagnosis of lymphonodal enlargements in the area of the liver and spleen hilium echotomography proved to be a valuable diagnostic method independent from endolymphatic methods. In X-ray treatments echotomography enables us to estimate the therapeutic result and to evaluate the lymphonodal status. The controls are performed in an out-patient manner.

[Radiotherapy under conditions of hyperbaric oxygen tension in a case of stage IV carcinoma of the cervix (author's transl)]. / Strahlentherapie in hyperbarem Sauerstoff bei Kollumkarzinom Stadium IV (kasuistischer Beitrag)

A case report is given of bilateral renal obstruction, uraemia and anaemia in a patient with carcinoma of the uterine cervix treated by Wertheim hysterectomy with bilateral tumour recurrence in the true pelvis. Combined therapeutic management - medical, urological and radiotherapeutic - brought about complete symptomatic improvement and clinical recovery of renal function. The significance of radiotherapy with ultra-hard photons under conditions of hyperbaric oxygen tension is stressed.

[Radiotherapeutic methods in the management of ovarian cancer (author's transl)]. / Methodik der strahlentherapeutischen Massnahmen beim Ovarialkarzinom.

A report is given of the therapeutic strategy and the stage-adjusted methods of irradiation in the treatment of ovarian cancer. The influence of radical surgery, irradiation and chemotherapy on survival rates is discussed and the results achieved in this unit, especially in patients admitted at a more advanced tumour stage, are presented.

[The place of ultrasonic diagnosis in radiotherapy]. / Ultraschalldiagnostik in der Strahlentherapie

1. Before starting radiotherapy ultrasonic investigation of the abdominal, retroperitoneal and pelvic area is mainly used to determine the stage of the disease, the tumour size and its relation to adjacent organs, as well as in the diagnosis of metastases. 2. During treatment, ultrasonography is useful in controlling the correct position of the treatment fields and the response of the tumour to treatment. 3. During follow up echography is helpful in controlling therapeutic results and in the early detection of tumour recurrence. At this point the procedure frequently replaces diagnostic X-ray control. 4. In regard to treatment planning, the outlines of the organs are directly transferred from the B-mode scan to the treatment plan. Hence, the position of the treatment fields and the isodose distribution can be exactly adjusted to e patient's anatomical requirements. Several examples are given to illustrate this procedure.

[Radiotherapy of ovarian carcinoma (author's transl)]. / Die Strahlentherapie des Ovarialkarzinoms

The difficulties of early diagnosis and therapeutic management of ovarian carcinoma are discussed. Large-field irradiation of the abdomen in stage II and III cases with Co-60 screen and pendular irradiation significantly improves the survival rate of the patients. In these cases radical operation combined with intensive postoperative irradiation with Co-60 gamma-rays is considered to be the treatment of choice. Above all, a focal dose of 6000 rad, which can be attained during inpatient treatment, leads to a marked improvement in the results.

[The significance of immunological investigations during radiotherapy for breast cancer (author's transl)]. / Bedeutung der immunologischen Untersuchung wahrend der Strahlentherapie des Mammakarzinoms.

The immune profile was controlled in 50 patients with breast cancer over a period of 5 years. No useful method for early detection, prognosis or exacerbation of disease could be developed from these findings for routine clinical work.

[Transurethral electroresection with postoperative betatron irradiation in bladder cancer: indication and results]. / Transurethrale Elektroresektion mit postoperativer Betatronbestrahlung bei Blasenkarzinom: Indikation und Ergebnisse.

100 patients suffering from infiltrating urinary bladder cancer underwent transurethral resection followed by external megavolt irradiation (Betatron) are presented. The value of irradiation and its role in the actual therapeutic concept is discussed. The results of the combined therapy in infiltrative urinary bladder cancer using transurethral resection and megavolt irradiation are demonstrated according to stage (T2, T3) and histological grading (G2, G3). The 5-years survival rate amounts around 80%, in deep infiltrating bladder cancer about 50%. The morbidity of postoperative megavolt therapy was negligible. The results are superior to megavolt therapy alone and approach the one achieved by radical surgery; in addition the possibility of salvage-cystectomy remains open.

[Optimum implementation of brachyradiotherapy in head and neck tumours (author's transl)]. / Optimierung der Brachycurietherapie im Kiefer-Gesichts-Bereich.

Modern techniques in brachyradiotherapy using moulds are described for various tumours of the head and neck. The ideal dose distribution can be calculated by the use of computers and practical examples are shown. The radiobiological and also economical advantages of this method of treatment are discussed.

[Studies on the immune status of patients with operated and irradiated cervical and breast cancer. III. Comparative investigation of the immune status of patients with breast cancer treated by operation and irradiation and of patients with cervical cancer treated either by operation or irradiation (author's transl)]. / Untersuchungen über den Immunstatus von operierten und von bestrahlten Fällen mit Kollum- und Mammakarzinom. III. Vergleichende Untersuchung über den Immunstatus von operierten und bestrahlten Fällen mit Mammakarzinom gegenüber bestrhlten und nichtbestrahlten Fällen mit Kollumkarzinom

The immunological reactivity of 19 operated cases of breast cancer (14 T1 2, 5T3) was investigated before and at 3-weekly intervals up to 12 weeks after radiotherapy by means of a large panel of techniques. The results were compared with two groups of identically-investigated patients, one consisting of 11 cases of cervical cancer (stage III), treated solely by irradiation and the other of 12 cases of cervical cancer (Stages I a and II b), treated by operation only. Before irradiation and in the non-irradiated group cellular immunity appeared to be more disturbed in cases of breast cancer than in cases of cervical carcinoma, as shown by the lowest number of lymphocytes, the lowest number of spontaneously-rosetting lymphocytes, the lowest percentage of DNCB sensitization in patients and the lowest percentage of Tuberculin-positive skin tests. In both types of carcinoma the humoral immunity appeared to be impaired, as apparent from the lowered immune response to tetanus vaccination. Other parameters of humoral immunity such as the immune globulin concentration, iso- and heteroagglutinine, the titre of measles antibodies or membrane fluorescence of lymphocytes showed no dinstinct trends during the investigation period. After irradiation a) inhibiting and b) stimulating influences were observed: a) The incidence and extent of the immune response to tetanus vaccination was further reduced and a distinct lymphopenic effect was observed. b) The incidence of positive skin tests with varidase, as well as the number of spontaneously-rosetting lymphocytes increased after the commencement of irradiation. Apart from the known sensitization with DNCB and skin tests with tuberculin, determination of the antitoxin titre before and after tetanus vaccination provided the most reliable results in regard to immunological reactivity in the investigated tumour patients.

[Simultaneous radio-chemotherapy of advanced epithelial ovarian cancer--results after three years (author's transl)]. / Simultane Radio-Chemotherapie bei fortgeschrittenen epithelialen Ovarialkarzinomen--Ergebnisse nach 3 Jahren.

An interdisciplinary prospective, non-randomized study was performed at the University Clinic for Radiotherapy and Radiobiology of Vienna in 26 patients with advanced epithelial ovarian cancers (FIGO stage III and IV) from February 1977 until February 1980. All patients underwent a combined radiotherapy-chemotherapy programme. In those 12 patients in whom at the time of the first operation only a biopsy was possible, the aim was to achieve early operability for a second-look operation (with removal of the internal reproductive organs, the omentum and remaining tumour masses). In 8 of theses 12 patients it was technically possible to perform radical surgery or to reduce tumour masses to under 2 cm. Of 20 evaluable patients 14 had stage III and 6 had stage IV cancer. In patients with stage III the response rate was 100% and the complete remission rate (with or without second-look operation) was above 70%. The duration of complete remission exceeded 10 months, median survival is at present 17 months. Patients with stage IV had a response rate of 66% (but mainly partial remissions), with significantly shorter survival times. Bowel complications occurred in one quarter of the patients and led to a revision of our therapeutic concept and the time sequence of the combined modality treatment. The importance of significant prognostic factors is stressed. The study indicated the superiority of the combined treatment approach in patients with stage III cancer. Patients with stage IV cancer, are, on the other hand, best managed primarily by chemotherapy; palliative irradiation and a second-look operation should be reserved only for selected patients.

[The moving-strip technique in the treatment of ovarian cancer (author's transl)]. / Die Durchführung der Moving-strip-Technik (Streifentechnik) bei der Behandlung von Ovarialkarzinomen.

A critical analysis of the latest results in the treatment of epithelial ovarian carcinomas indicates significant progress. Postoperative radiotherapy using the moving-strip technique is the treatment of choice in stages I a (grade 2 and 3 lesions and/or tumour rupture), Ib, II and III (asymptomatic) with residual tumours less than 2 cm in size. In the stages Ic, IIc and III (symptomatic) with residual tumours larger than 2 cm, radiotherapy may be curative following successful initial combination chemotherapy. This combined modality treatment is being investigated in our department in a prospective trial. The importance of prognostically significant factors (completeness of operation, age, histology, histological grade and adequate treatment) is discussed. The moving-strip technique is described in particular with regard to its practical application as basis of the modern therapeutic regimen for ovarian cancer.

[Male breast cancer]. / Das männliche Mammakarzinom.

Between 1974 and 1982 inclusive 18 male patients were treated for breast carcinoma. 12 patients had postoperative radiotherapy whereas 4 were referred for treatment of recurrent or metastatic disease. One patient showed signs of inflammatory breast cancer and was treated with chemo-radiotherapy and one was being followed up in our department after radiotherapy for prostatic cancer in 1970. Median overall survival was 52 months and the median disease-free interval was 21 months.

[Flow cytometric measurements of in vivo incorporated bromodeoxy- uridine into the DNA of experimental and human tumors]. / Flusszytometrische Messungen von in vivo inkorporiertem Bromodeoxyuridin (BUdR) in die DNA von experimentellen und menschlichen Tumoren.

A new cell kinetic method was used in vivo in an experimental mouse tumour and in human tumours of the oral cavity for the first time. The incorporation of BUdR into cells in the S-phase that are actively synthesizing DNA enables the determination of the rate of DNA synthesis from the amount of BUdR-related fluorescence using monoclonal antibody and the proportion of S-phase cells which are actively engaged in synthesis. The application of BUdR to the patients and the preparation of the tumour is reported.

[Investigations on the immune status of operated and irradiated cases of cervical and breast cancer I. immune status before and after surgery of cancer of the cervix, stages I b and II a(author's transl)]. / Untersuchungen ürber den Immunstatus von operierten und von bestrahlten Patientinnen mit Kollum- und Mammakarzinom I. Immunstatus vor und nach Operation von Kollumkarzinomen der Stadien I b und II a

12 patients were investigated in regard to their state of humoral immunity by means of the following determinations: IgG, IgM, and IgA concentrations in the serum, hetero- and isoagglutinins, tetanus antitoxin before and after immunization with toxoid measles antibodies and the percentage of lymphocytes with membrane fluorescence. The cellular immunity was investigated in some patients with determination of the percentage of spontaneously-rosetting lymphocytes, of the DNCB skin-test reactivity before and after sensitization with DNCB and of skin-test reactivity to candida, trichophyton, varidase, OT and staphylo antigen. The functional efficiency of polymorphonuclear leucocytes was investigated by means of the NBT test and Staph. aureus, E. coli and Latex particles. All investigations were performed before, and 3, 6, 9 and 12 weeks after surgery. 4 methods only amongst the entire spectrum employed in the investigation proved to give sufficient evidence of signs of decreased efficiency of the immune response in the investigated patients: determination of tetanus antitoxin before and after immunization, a distinct increase in titre being observed only in 5 cases, determination of the sensitization to DNCB, which was positive only in 4 cases and determination of skin-test reactivity to varidase and OT, which was found to be less frequently positive than in controls. However, all these reactions showed no evidence of any correlation to surgical management and appeared merely to reflect characteristic responses of these cancer patients. Moreover, with the exception of the decrease in lymphocytes, no changes were detected in the data obtained by the other methods used in this study which might show some reflection of an alteration in response following surgery.

[Irradiated cases of cervical and breast cancer II. Comparative investigation of the immune status of irradiated cases with stage III cancer of the cervix and operated, non-irradiated cases (author's transl)]. / Utersuchungen über den Immunstatus von operierten und von bestrahten Fällen mit Kollum- und Mammakarzinom

Eleven patients with stage-III cancer of the cervix were investigated before, during and after radio-therapy in regard to their state of humoral immunity on the basis of determinations of the serum IgG, IgM and IgA concentration, of hetero- and isoagglutinins, of tetanus antitoxin before and after vaccination with toxoid, of measles antibodies and of the percentage of lymphocyte membrane fluorescence. The cellular immunity of the same patients was investigated by determination of the percentage of spontaneously-rosetting lymphocytes, of skin-test reactivity with DNCB before and after sensitization, of skin-test reactivity with candida, trichophyton, varidase, OT and staphylo antigen. The function of polymorpho-nuclear leucocytes was investigated by means of the NVT test and St. aureus, E. coli and latex particles. All investigations were performed both before, and 3, 6, 9 and 12 weeks after the commencement of radiotherapy and the results were compared with those of an operated, non-irradiated group (stages I b and II a). Two types of noteworthy results were observed: 1. A decrease in immunological reactivity, probably in connection with cancer, since this reaction was observed both in irradiated and in non-irradiated cases, characterized by lowered or absent immune answer to tetanus toxoid, lymphopenia, decrease in sensitization to DNCB and less positive skin tests to old tuberculin and varidase. 2. An additional inhibition (although in one investigation stimulation of the immune answer was also seen), probably in connection with radiotherapy, characterized by an additional decrease in immune answer to tetanus toxoid, in skin sensitivity to DNCB sensitization and in tests with old tuberculin, and an augmented lymphopenia, as well as an increase in positive skin tests with varidase. No significant changes were observed with any other method.