Double-blind randomized dose-finding study in acute vulvovaginal candidosis. Comparison of flutrimazole site-release cream (1, 2 and 4%) with placebo site-release vaginal cream

A double-blind randomized comparative phase II study of flutrimazole site-release vaginal cream (1, 2 and 4%) with placebo site-release vaginal cream was undertaken in patients with acute vulvovaginal candidosis. Vaginitis was demonstrated by both positive findings on microscopic examination of vaginal smears and positive culture as well as by the presence of clinical signs and symptoms. The vaginal monodose treatment was inserted in the evening at bedtime using a vaginal applicator and, in addition, all four groups of patients received additional topical external cream for application to the vulva twice-daily for 7 days; the placebo group received a placebo cream and the active therapy groups all received a 2% flutrimazole cream. A total of 133 patients who were seen over a 10-month period were screened and randomized: five patients did not take the allocated medication, and four patients whose menstrual period began shortly after study entry were excluded from the study, leaving 124 patients who were randomly allocated to receive a monodose vaginal 1% cream (regimen A, 28 patients), a monodose vaginal 2% cream (regimen B, 32 patients), a monodose vaginal 4% cream (regimen C, 31 patients) or a monodose vaginal placebo cream (regimen D, 33 patients). At the assessment 9 days after the end of therapy the proportion of patients who were cured was 82% in group A, 87.4% in group B, 83.8% in group C and 63.5% in group D. Three patients (10.7%) in group A, four (12.5%) in group B, one (3.2%) in group C and 12 (36.36%) in group D did not respond to the treatment. One patient (3.5%) in group A, and two patients (6.4%) in group C terminated the treatment prematurely due to intolerance. There was a significant association between Candida glabrata and treatment failure (P < 0.04) and C. glabrata and carrier state (P = 0.01) in vagina (chi 2 test, P = 0.01) and vulvovagina (chi 2 test, P = 0.00001). At the assessment 4 weeks after the end of therapy the proportion of cured patients was 60.6% in group A, 78% in group B, 80.6% in group C and 48.4% in group D. Group D (placebo) versus group B (2%) and group C (4%) showed a significant difference (P = 0.01 and P = 0.007, respectively). Although there were no significant differences in clinical and mycological activity between the three active groups, group B (flutrimazole 2% site-release vaginal cream) was chosen for clinical use due to its tolerance profile. Seven patients (25%) in group A, three (9.3%) in group B, two (6.4%) in group C and five (15.1%) in group D relapsed 4 weeks after the end of therapy; the relapse rate was not significantly associated with positive culture results 9 days after treatment. There was a significant association between C. glabrata and the carrier state (P < 0.01). The overall ineffective treatment (includes failures at control 1, relapses at control 2 and premature terminations) was 39% in group A, 21.7% in group B, 16% in group C and 51.3% in group D. There was a significant difference in the overall ineffective treatment when C and D groups were compared with placebo (P = 0.01 and P = 0.003, respectively).     

A clinical multicenter study comparing efficacy and tolerability of topical combination therapy with clotrimazole (Canesten, two formats) with oral single dose fluconazole (Diflucan) in vulvovaginal mycoses

Two topical formats containing clotrimazole [500 mg single dose vaginal tablet (VT) or 10% single dose vaginal cream (VC) for intravaginal use] combined with additional clotrimazole cream for topical application to the vulval area (Canesten 1 Combi, Bayer AG, Leverkusen, Germany) were compared with oral fluconazole 150 mg single dose treatment of vulvovaginal mycosis (VVM) in a single-blind clinical study. The objective of the study was to demonstrate the equivalent efficacy of the clotrimazole combination therapies (VT + 1% cream and VC + 2% cream), and fluconazole 150 mg oral capsule (Diflucan 1, Pfizer Gmbh, Karlsruhe, Germany) in terms of overall response defined as clinical cure and mycological resolution. Overall, combination therapies containing either clotrimazole 500 mg VTs or clotrimazole 10% VC were as effective as a single dose fluconazole 150 mg oral tablet in treating VVM with rates for overall response being 66%, 61% and 60%, respectively, after 14 days. There were no significant differences in the time to onset of symptom relief in the clotrimazole 500 mg tablet group and clotrimazole 10% VC compared with fluconazole 150 mg oral capsules. Only 50% of 88 patients across treatment groups with mycological recurrence also experienced return of symptoms over the entire 8 week follow-up period. All treatments administered were safe and well-tolerated and the number of patients experiencing adverse events was low.     

Clinical and mycological efficacy of single-day oral treatment with itraconazole (400 mg) in acute vulvovaginal candidosis

This study aimed to investigate the effectiveness of single-day oral treatment with itraconazole in acute vulvovaginal candidosis (VVC). Vaginitis was demonstrated by both detection of yeast cells and pseudohyphae formation on microscopic examination of vaginal discharge and mycological culture as well as by the clinical signs and symptoms. Clinical and mycological examinations of the 52 patients were performed before, 1 week (short-term) and 4 weeks (long-term) after single-day oral treatment with itraconazole 200 mg b.i.d. The causative yeast fungi were: Candida albicans (76.9%), C. glabrata (9.6%), C. kefyr (9.6%) and C. krusei (3.9%), respectively. In short- and long-term examinations, clinical cure rates were found to be 61.5% and 90.4%, and mycological cure rates were 63.5% and 90.4%, respectively. Itraconazole was found to be 95.0% effective with C. albicans and 75.0% with other Candida species. It is concluded that treatment of acute VVC with itraconazole is safe and effective in the long-term.     

The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis

To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7–14 follow‐up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30–35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7–14 follow‐up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30–35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder.     

Guideline vulvovaginal candidosis (2010) of the German Society for Gynecology and Obstetrics, the Working Group for Infections and Infectimmunology in Gynecology and Obstetrics, the German Society of Dermatology, the Board of German Dermatologists and the German Speaking Mycological Society

Candida (C.) species colonize the estrogenized vagina in at least 20% of all women. This statistic rises to 30% in late pregnancy and in immunosuppressed patients. The most often occurring species is Candida albicans. Host factors, especially local defense deficiencies, gene polymorphisms, allergic factors, serum glucose levels, antibiotics, psychosocial stress and estrogens influence the risk for a Candida vulvovaginitis. In less than 10% of all cases, non-albicans species, especially C. glabrata, but in rare cases also Saccharomyces cerevisiae, cause a vulvovaginitis, often with fewer clinical signs and symptoms. Typical symptoms include premenstrual itching, burning, redness and non-odorous discharge. Although pruritus and inflammation of the vaginal introitus are typical symptoms, only less than 50% of women with genital pruritus suffer from a Candida vulvovaginitis. Diagnostic tools are anamnesis, evaluation of clinical signs, the microscopic investigation of the vaginal fluid by phase contrast (400 x), vaginal pH-value and, in clinically and microscopically uncertain or in recurrent cases, yeast culture with species determination. The success rate for treatment of acute vaginal candidosis is approximately 80%. Vaginal preparations containing polyenes, imidazoles and ciclopiroxolamine or oral triazoles, which are not allowed during pregnancy, are all equally effective. C. glabrata is resistant to the usual dosages of all local antimycotics. Therefore, vaginal boric acid suppositories or vaginal flucytosine are recommended, but not allowed or available in all countries. Therefore, high doses of 800 mg fluconazole/day for 2-3 weeks are recommended in Germany. Due to increasing resistence, oral posaconazole 2 × 400 mg/day plus local ciclopiroxolamine or nystatin for 15 days was discussed. C. krusei is resistant to triazoles. Side effects, toxicity, embryotoxicity and allergy are not clinically important. A vaginal clotrimazole treatment in the first trimester of pregnancy has shown to reduce the rate of preterm births in two studies. Resistance of C. albicans does not play a clinically important role in vulvovaginal candidosis. Although it is not necessary to treat vaginal candida colonization in healthy women, it is recommended in the third trimester of pregnancy in Germany, because the rate of oral thrush and diaper dermatitis in mature healthy newborns, induced by the colonization during vaginal delivery, is significantly reduced through prophylaxis. Chronic recurrent vulvovaginal candidosis requires a "chronic recurrent" suppression therapy, until immunological treatment becomes available. Weekly to monthly oral fluconazole regimes suppress relapses well, but cessation of therapy after 6 or 12 months leads to relapses in 50% of cases. Decreasing-dose maintenance regime of 200 mg fluconazole from an initial 3 times a week to once monthly (Donders 2008) leads to more acceptable results. Future studies should include candida autovaccination, antibodies against candida virulence factors and other immunological trials. Probiotics should also be considered in further studies. Over the counter (OTC) treatment must be reduced.     

Ein-Dosis-Therapie von Vaginalmykosen mit Clotrimazol-Vaginalcreme 10%/Single-Dose Therapy of Vaginal Mycoses with Clotrimazole Vaginal Cream 10%

Zusammenfassung: In zwei Beobachtungsstudien und im randomisierten Vergleich gegen Clotrimazol-Vaginaltabletten 500 mg wurde bei 230 Patientinnen mit kulturell nachgewiesener Vaginalmykose Clotrimazol-Vaginalcreme 10% geprüft. In 148 Fällen wurde mit Vaginalcreme behandelt. Von dieser waren einmalig 5 g (500 mg Clotrimazol) durch den behandelnden Arzt appliziert worden. In der Vergleichsstudie ergab sich für die Creme-Behandlungsgruppe bei der 1. (2.) Kontrolluntersuchung eine kulturelle Heilungsrate von 85% (73%). In der Tabletten-Gruppe lag sie bei 87 % (80 %). Die klinische Heilungsrate betrug zu den Untersuchungszeitpunkten 94% (85%) in der Creme-Gnippe und 91 % (94%) in der Tabletten-Gruppe. In den Beobachtungsstudien waren die kulturellen Heilungsraten mit 84 % (Studie I) und 87 % (Studie II) eine Woche nach Therapieende sowie vier Wochen nach Therapieende mit 80% und 83 % ähnlich. Bei der klinischen Therapiebeurteilung konnte eine Woche nach Therapieende ein Therapieerfolg bei 100% bzw. 83 % der Patientinnen festgestellt werden. Vier Wochen nach Therapieende lagen die klinischen Heilungsraten bei 92 % und 90%. Die lokale Verträglichkeit der Clotrimazol-Vaginalcreme 10 % war gut. Summary: Clotrimazole vaginal cream 10% was tested in 230 patients with culturally proved vaginal mycosis in two observation studies and in one randomised comparative study against clotrimazole vaginal tablets 500 mg. 148 patients were treated with vaginal cream. In these cases a single dose of 5 g cream (500 mg clotrimazole) was applied by the attending physician. In the comparative study cultural cure rates of 85% (73 %) were observed for the cream group at the 1st (2nd) check-up. In the tablet group there were cure rates of 87 % (80 %). The clinical cure rates were 94 % (85%) in the cream group an 91 % (94%) in the tablet group at the times of check-up. In the observation studies the cultural cure rates with 84 % (study I) and 87 % (study II) one week after treatment were similar to those recorded 4 weeks after treatment with 80% and 83%. At the clinical assessment a success of 100 % and 83 % respectively could be demonstrated one week after treatment. 4 weeks after treatment the clinical cure rates were 92 % and 90 %. The local tolerance of clotrimazole vaginal cream 10% was good.     

优福定联合叶酸片口服治疗晚期胃癌34例临床观察

目的　观察优福定(UFT)联合叶酸片口服治疗晚期胃癌的疗效。　方法　34例晚期胃癌,按不同的叶酸剂量分为A组18例(UFT12片/d;叶酸片60mg/d)B组16例(UFT12片/d;叶酸片30mg/d)。其中初治23例,复治11例。　结果　34例中,总有效率3825%。A组有效率3889%(完全缓解CR2例,部分缓解PR5例);B组有效率3750%(CR1例,PR5例)。两组疗效无明显差异(P>005)。有效病例中位缓解期4个月。本方案毒副反应小,患者能耐受。　结论　UFT联合叶酸片口服方案近期疗效高,毒副反应低     

Econazole-polycarbophil, a new delivery system for topical therapy: microbiological and clinical results on vaginal candidiasis

The aim of this study was to demonstrate that the addition of a bioadhesive polymer to econazole, which increases the duration of the active drug at the site of infection, leads to a greater frequency of negative culture after treatment and probably reduces the recurrence rate of vaginal candidiasis.180 women with vaginal candidiasis were treated with 150 mg vaginal ovules econazole nitrate with (group A) or without (group B) polycarbophil. After 3 days of treatment the negative culture of Candida albicans reached 98.6% in group A and 84.8% in B group, while the overall persistence (C. albicans, C. glabrata, C. krusei, and C. parapsilosis) was 5.6% and 30%, respectively. During a 60-day follow-up, only one case out of 85 (1.2%) in group A reported recurrence while in group B there were 6 out of 63 (9.5%) recurrences. We conclude that, since the women were treated with the same amount of econazole, the better clinical and microbiological results can be attributed to polycarbophil, as confirmed by a significant reduction of recurrences.     

Antifungal susceptibility testing in chronically recurrent vaginal candidosis as basis for effective therapy

The chronically recidivist vulvo-vaginal candidiasis is one of the most stubborn problematic diagnosis in the dermatology and gynaecology ward. Prognosis and therapy are primarily determined by the causative micro-organism and the interaction of the fungal species with the currently available antifungal agents. Objective of the study was the investigation of vaginal yeast isolates from patients with chronically recidivist vaginal candidiasis against 8 antifungal agents with the aim of optimising the standard therapy with azole antifungal agents and assessment of alternative therapy schemes. 55 clinical isolates (Dermatology, Charité) of 40 patients were tested by microdilution according to DIN 58940-84. Species differentiation and identification was performed by Fourier-Transform Infrared Spectroscopy (FTIR). In the result Candida glabrata was the predominant causative agent for the recidivist vaginal candidiasis. MIC-mode values for C. glabrata were: fluconacole 32 micrograms/ml, itraconacole 1 microgram/ml, ketoconacole 1 microgram/ml, amphotericine B, voriconacole 0.03 microgram/ml, amphotericin B 0.5 microgram/ml, terbinafine 128 micrograms/ml, cicloproxolamine 4 micrograms/ml, 5-fluorocytosine 0.03 microgram/ml. Some strains of Patients with suboptimal introductory low doses of fluconacole showed increasing of MIC in course of therapy. Parallel resistance with itraconacole was observed in all these cases. Consecutively isolated strains could be clearly and reliably identified by FTIR. In conclusion of most importance is the initial dose adapatation of the drug used, e.g. for fluconacole 800/d p.o., when C. glabrata is the causative agent. Low dose fluconacole therapy is always unsuccessful in recurrent vaginal candidiasis and induces secondary resistance. Demonstrated high susceptibility of voriconacole, amphotericine B an 5-fluorocytosine particularly for C. glabrata may indicate of an anitmycotic therapy potential unconsidered regarding to dermatological indication up to now.     

Patient‐reported outcomes from two randomised studies comparing once‐weekly application of amorolfine 5% nail lacquer to other methods of topical treatment in distal and lateral subungual onychomycosis

Patient adherence is a key consideration in the choice of a topical regimen for the treatment of onychomycosis. The objective of this study was to investigate patient‐reported outcomes (treatment utilisation, adherence and satisfaction) in onychomycosis treated with once‐weekly amorolfine 5% nail lacquer versus once‐daily ciclopirox 8% nail lacquer (Study A) or once‐daily urea 40% ointment/bifonazole 1% cream combination regimen (Study B). Study A: Subjects received amorolfine and ciclopirox on opposite feet for 12 weeks. Study B: Subjects received amorolfine and urea/bifonazole on opposite feet for 6‐7 weeks. Assessments included subject adherence as per label, treatment preference and questionnaire. Study A: More subjects adhered to amorolfine (85%) than to ciclopirox (60%) (P = .025). Overall, subjects were satisfied (95% vs 100%, respectively) and the treatments were balanced in terms of preference (50% vs 45%) at week 12. Study B: More subjects adhered to amorolfine dosage (81.8%) than to the dosage of the urea/bifonazole combination regimen (59.1%) (P = .096). At the end of study, 85.7% of subjects preferred amorolfine versus 14.3% for urea/bifonazole. Fewer subjects experienced local side effects with amorolfine (4.5%) compared to urea (27.3%) and bifonazole (15%). Amorolfine 5% nail lacquer offers a simple and convenient treatment option, which may result in improved patient adherence and consequently lead to improved efficacy and patient satisfaction.     

Clinical and bacteriologic efficacy of amoxycillin b.d. (45 mg/kg/day) versus amoxycillin t.d.s (40 mg/kg/day) in children with group A beta-hemolytic streptococcal tonsillopharyngitis

This randomized, observer-blind, multicenter, parallel-group study compared the clinical and bacteriologic efficacy and safety of amoxycillin, 45 mg/kg/day b.d. and amoxycillin, 40 mg/kg/day t.d.s. after 7 days of treatment in 517 children with acute bacterial tonsillopharyngitis. At the end of treatment, a successful clinical response was recorded in more than 96% of patients in each of the treatment groups. A similar result was obtained at follow-up. Among those patients who were bacteriologically evaluable at the end of treatment, a successful bacteriologic response was achieved in more than 94% in each treatment group. Both treatments were well tolerated. Drug-related adverse events were recorded in just 12 patients (4.6%) in the b.d. group and six (2.4%) in the t.d.s. group. The study demonstrated that a twice-daily regimen of amoxycillin, 45 mg/kg/day, was as effective and as well tolerated as the standard three-times-daily regimen of amoxycillin, 40 mg/kg/day, in the treatment of acute bacterial tonsillopharyngitis in children.     

Combination therapy with cisplatin, 5'-deoxy-5-fluorouridine (5'-DFUR) and mitomycin (MMC) in patients with inoperable, advanced gastric cancer

The optimal dose of cisplatin (CDDP) for combination chemotherapy for the treatment of inoperable, advanced gastric cancer has yet to be established. We therefore performed a randomized study to compare the therapeutic usefulness of two dose levels of cisplatin. 5'-deoxy-5-fluorouridine (5'-DFUR 1,400 mg/m(2)/d) was given orally on days 1 to 4 and 15 to 18. Mitomycin C (MMC, 5.75 mg/m(2)/d) was injected intravenously on day 5. In addition, 80 mg/m2/d of CDDP (regimen A) or 60 mg/m(2)/d of CDDP (regimen B) was given by 2-h intravenous drip infusion on day 5. This treatment cycle was repeated every four weeks. Fifty-six patients were enrolled. Clinical response was evaluated in 32 patients (regimen A, 16 patients; regimen B? 16 patients) with measurable lesions. The response rate was significantly higher with regimen A (9 PR/16, 56.3%) than with regimen B (3 PR/16, 18.9%) (p=0.028, chi(2) test). Median survival was slightly but not significantly longer with regimen A (7.4 months) than with regimen B (6.3 months). Drug toxicity included myelosuppression and gastrointestinal symptoms, but there were no serious adverse reactions or differences in safety between the treatment regimens. Regimen A was associated with a high response rate and low toxicity. The optimal dose of CDDP in combination with 5'-DFUR and MMC for the treatment of advanced gastric cancer is regarded to be 80 mg/m(2).     

Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood (JCCLSG-S811). The Japanese Children's Cancer and Leukemia Study Group

From 1981 to 1983, 131 previously untreated patients with acute lymphoblastic leukemia (ALL) standard-risk group were entered to the protocol JCCLSG-S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by treatment with prednisone (PRD) plus vincristine (VCR) or vindesine (VDS). After preventive central nervous system (CNS) therapy including 18 Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were assigned randomly to the two maintenance chemotherapies, Regimen A and Regimen B. Regimen A (intermittent regimen) consisted of PRD (120 mg/m2/day by mouth for 5 days) plus 6-mercaptopurine (6MP) (175 mg/m2/day by mouth for 5 days) plus VCR (2.0 mg/m2 intravenously) alternating biweekly with MTX (225 mg/m2 intravenously). Regimen B (continuous regimen) consisted of 6MP (50 mg/m2/day by mouth) plus MTX (20 mg/m2/week by mouth) combined with pulses of PRD and VCR (the same dosages as Regimen A) every 4 weeks. As the late intensification therapy (LIT), five courses of high-dose MTX (2000 mg/m2 per dose per week intravenously for three doses every 12 weeks) with leucovorin rescue were administered to all patients who were in continuous complete remission (CCR) for more than 2 years. Sixty and 55 patients, respectively, were registered in Regimen A and B. The CCR rates in Regimen A and B were 75.1% +/- 5.8% (mean +/- 1 SE) and 49.7% +/- 7.3% (P less than 0.01) at 4 years, and 72.1% +/- 6.3% and 49.7% +/- 7.3% (P less than 0.05) at 5 years, respectively. In Regimen B, CNS and testicular relapses increased after 3 years of CCR. In addition, the patients in Regimen B had a much higher incidence of infections than Regimen A. The LIT did not seem to have important effects on the duration of CCR. From these data we conclude that the intermittent cyclic regimen of 6MP and MTX may be more effective as compared to the continuous administration of these drugs in the maintenance chemotherapy.     

奥沙利铂治疗结直肠癌的随机多中心Ⅱ期临床试验

Objective: To evaluate the efficacy and safety of Oxaliplatin in the patients with colorectal cancer. Methods: In a multicenter randomized control study, a total of 144 patients were divided into four groups: Oxaliplatin (Haitong) 5-FU, CF(group A) 41 cases; 5-FU CF (group B) 41 cases; Oxaliplatin (Haitong) 5-FU, CF (group C) 31 cases; Oxaliplatin (positive drug) 5-FU CF (group D) 31 cases. Oxaliplatin combination regimen: L-OHP 130 mg/m2 i.v. infusion 2 h d1; CF 200 mg/m2i.v. 2h d1-d5; 5-FU 300 mg/m2 i.v. infusion 4h d1-d5 (after CF). 5-FU CF combination regimen: CF 200 mg/m2 i.v. infusion 2 h d1-d5, 5-FU 300 mg/m2 i.v. infusion 4h d1-d5 (after CF), the schedule was repeated every 3 weeks. The total cycles were 3. Results: After three circles treatment, overall response rate of 4 groups was 24.4% (group A), 2.4% (group B), 25.8%(group C) and 19.4% (group D), respectively. The response rate was significantiy different between group A and group B (P＜0.01), but no significant difference was observed between group C and group D (P＞0.05). Conclusion: The Oxaliplatin(Haitong) for injection combination regimen is effective in the treatment of colorectal cancer.     

Usefulness of pharmacokinetic modulating chemotherapy (PMC) for the postoperative adjuvant therapy of colorectal carcinoma: a preliminary report

Pharmacokinetic modulating chemotherapy (PMC) using oral UFT and continuous venous 5-FU infusion was administered to 22 resectable patients with Dukes' B2-D colorectal carcinomas. The regimen was arranged as follows: Group A (n = 12) UFT 300-450 mg/day, 5 days a week and 5-FU 440-600 mg/m2/24 hr (750-1,000 mg/body/24 hr) once a week, Group B (n = 10), UFT less than 300 mg/day, 5 days a week, and/ or 5-FU less than 440 mg/m2/24 hr (750 mg/body/ 24 hr) once a week. The control group (Group C, n = 26) was selected at random from among non-PMC cases matched for other background factors and in which surgery had been performed during the past 4 years. Fifteen out of 26 patients in Group C were treated with 5-FU masked compounds orally. The cumulative 2 year recurrent rates of Groups A, B and C were 8.3%, 52.0% and 50.0%, respectively; the rate of Group A was significantly lower than that of Group B (p < 0.05). Four patients who suffered from PMC-related side effects of grade 1-2 wanted to decrease their dosage of UFT and/or 5-FU. They were registered in Group B. These results suggest that the regimen of Group A was advantageous in improving the prognosis after resection of Dukes' B2-D colorectal carcinoma.     

Fluconazole in the treatment of oropharyngeal candidosis in HIV-positive patients

106 HIV-positive patients with 129 episodes of oropharyngeal Candida infection were treated with fluconazole (50-300 mg/d). Treatment lasted from 4 to 23 days. The majority of patients were in more advanced stages of HIV infection (82% AIDS cases). Therapy with fluconazole led to complete healing or improvement of clinical symptoms in 93% of all treatment courses. However, according to cultural findings, an elimination or recession of pathogens was achieved in only 70% of cases. Cultural monitoring showed a slow reduction of pathogens, as opposed to a fairly rapid clinical improvement. Candida albicans was the most frequently isolated Candida species (n = 128); the most selected Candida species during treatment were C. glabrata, C. krusei, and C. inconspicua. It is remarkable that C. glabrata, a low-grade pathogen, caused enanthema in 2 patients and a typical oral thrush in 1 patient. Fluconazole was well-tolerated, and apart from mild gastro-intestinal symptoms in 1 patient, no severe side effects were observed.     

New multiple-agent chemotherapy (B-DOPA) for advanced Hodgkin's disease.

B-DOPA (Bleomycin (B), D-imidazole carboxamide (D), Oncovin (O), Prednisone (P), Adriamycin (A) is a program developed for the treatment of Hodgkin's disease resistant to MOPP therapy. Twenty unselected patients were treated by the following dose schedule: B, 4 mg/m2 days 2 and 5; D, 150 mg/m2 days 1 to 5; O (vincristine), 1.5 mg/m2 days 1 and 5; P, 40 mg/m2 days 1 to 6; A, 60 mg/m2 day 1. Each course, was repeated at 3 to 4 week intervals to maximum adriamycin dose of 450 mg/m2. All patients had received prior MOPP therapy and six had received prior radiotherapy. Fifteen of the 20 patients entered into the study were evaluable for response. There were nine (60%) complete responders and three (20%) partial responders. The median duration of complete remission was 14+ months with six of nine patients remaining in remission to a maximum of 21 months. The median survival of the nonresponders was 3 months. B-DOPA is an effective combination chemotherapy regimen for advanced Hodgkin's disease in patients who have previously received MOPP treatment, including patients who are refractory to MOPP therapy. The B-DOPA program or modifications thereof, may be integrated into primary treatment programs for advanced Hodgkin's disease.     

Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versuspaclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): A multicenter randomized trial

Purpose:The combination of paclitaxel and carboplatin has becomea widely used regimen in NSCLC due to phase II reports of moderate toxicity,reasonable activity and easy outpatient administration. Purpose of our presentprospective study was to evaluate the dose–response relationship ofpaclitaxel. Patients and methods:Since July 1996, 198 patients withnon-operable NSCLC and measurable disease without previous chemotherapyentered the trial. Ninety nine patients (group A) were randomized to receivepaclitaxel 175 mg/m² in three-hour infusion plus carboplatin dosedto an area under the concentration–time curve of 6 every 3 weeks and 99(group B) to receive the same regimen with paclitaxel increased to 225mg/m². Eligibility criteria included WHO performance status0–2, documented inoperable stage IIIA and IIIB, IV, no brain metastasis,no prior chemotherapy and adequate renal and hepatic function. Patients inboth groups were well-matched with baseline disease characteristics. Results:In group A with 90 evaluable patients, the response ratewas 25.6%(6 CR, 17 PR) whereas in group B with 88 evaluable patients,the response rate was 31.8% (3 CR, 25 PR),P = 0.733. Mediantime to progression favored the high-dose paclitaxel (4.3 vs. 6.4 months,P = 0.044). The median survival was 9.5 months for group A versus11.4 months for group B (P = 0.16). The one-year survival was37% for group A and 44% for group B (P = 0.35). Thebest prognostic factor for one-year survival was the response rate (P< 0.0001). With a relative dose intensity of paclitaxel 0.94 in bothgroups, neurotoxicity (P = 0.025) and leucopenia (P = 0.038)were more pronounced in group B patients. No toxic death was observed. Conclusions:Higher dose paclitaxel prolongs the median time toprogression but causes more neurotoxicity and leucopenia. The better responserate, the longer overall and better one-year survival seen with the higherdose of paclitaxel are not statistically significant.     

盐酸羟考酮控释片联合加巴喷丁治疗晚期癌症神经病理性疼痛疗效分析

目的:探讨盐酸羟考酮控释片联合加巴喷丁治疗晚期癌症神经病理性疼痛的疗效.方法:晚期癌症的神经病理性疼痛患者,通过视觉模拟划线法(VAS)和口头叙述法(VRS)分级进行疼痛强度评估,分为A组盐酸羟考酮控释片20例,B组盐酸羟考酮控释片+加巴喷丁20例,通过个体化用药,研究其治疗疼痛缓解度,有效率.结果:A组轻度疼痛9例,无痛6例,有效率为75.0％,B组轻度疼痛5例,无痛13例,有效率为90.0％.结论:盐酸羟考酮控释片+加巴喷丁治疗晚期癌症神经病理性疼痛疗效显著.     

Comparative Study of Apo-Cetirizine Single Therapy and Intermittent Sequential Therapy with Cetirizine,Loratadine and Chlorpheniramine in Allergic Rhinitis

There are limited numbers of articles, studying combined use of antihistamines. In this study, we compare single therapy of Apo-Cetirizine with a new regimen of intermittent sequential therapy with cetirizine, loratadine and chlorpheniramine in treatment of seasonal allergic rhinitis. This randomized clinical trial was performed between April and September at the peak prevalence of seasonal allergic rhinitis. Fifty-four eligible patients diagnosed clinically to have seasonal allergic rhinitis were randomized in two groups: 24 cases in single therapy arm, received Apo-Cetirizine 10 mg tablet daily and in other arm, 30 patients received sequential regimen of cetirizine 10 mg tablet, loratadine 10 mg tablet and chlorpheniramine 4 mg tablet, one tablet each day. Major Symptom Complex Score (MSCS) and Total Symptom Complex Score (TSCS) of patients were recorded before treatment and after 30 days of treatment in two groups. The average post-treatment MSCS and TSCS in combination therapy group showed better improvement than single therapy group but difference was not statistically significant (p value = 0.053 and p value = 0.104 respectively). Combination therapy regimen was better in improvement of nasal congestion (p value = 0.006). There were no significant difference between two groups in efficacy, side effects and patient’s satisfaction. Combination therapy would be effective on a wide spectrum of symptoms with lower price and theoretically offers lower chance of tolerance and re-appearance of complaints.