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Biomedical subjects

P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 55 records · Page 3Linked to original sources
PubMed1997

Randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with cancer.

PURPOSE: To investigate the antiemetic effect and tolerability of the 5-hydroxytryptamine3(5-HT3) antagonist ondansetron plus the dopamine D2 antagonist metopimazine versus ondansetron alone in patients receiving platinum-based chemotherapy. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients who were scheduled to receive two consecutive courses of platinum-based chemotherapy were randomized between ondansetron 8 mg intravenously (IV) followed by 8 mg orally twice a day plus metopimazine 35 mg/m2 as a 24-hour continuous infusion followed by 30 mg orally four times a day for 4 days, or ondansetron plus placebo. The study used a double-blind, crossover, placebo-controlled design. RESULTS: Ninety-four patients completed the crossover. Complete response (CR; no emetic episodes) was obtained on day 1 in 77.7% of the patients who received the combination versus 50.0% of those who received ondansetron alone (P = .00002), and in 51.7% versus 31.0% on days 2 to 6 (P = .0009). The overall CR (days 1 to 6) was 48.9% versus 25.3% (P = .0002). Additionally, significantly less nausea was observed with the combination on day 1 (P = .0002), days 2 to 6 (P = .0001), and days 1 to 6 (P = .00004). Patient preference was 63.6% for the combination and 13.6% for ondansetron alone; 22.7% expressed no treatment preference (P < .0001; therapeutic gain 50.0%; 95% confidence interval [CI], 31.6% to 68.4%). Adverse reactions were mild and without significant differences between the two treatments. CONCLUSION: Metopimazine plus ondansetron was significantly superior to ondansetron alone, concerning all efficacy parameters assessed, in patients who received platinum-based chemotherapy.

Adult↗
PubMed1997

Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group.

PURPOSE: To assess activity and toxicity of topotecan in previously treated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients with measurable SCLC, progressive after one first-line regimen, were eligible for the study. Two groups of patients were selected: (1) patients who failed first-line treatment < or = 3 months from chemotherapy discontinuation (refractory group); and (2) patients who responded to first-line treatment and progressed greater than 3 months after chemotherapy discontinuation (sensitive group). Topotecan was administered as a 30-minute daily infusion at a dose of 1.5 mg/m2 for 5 consecutive days, every 3 weeks. RESULTS: One hundred one patients were entered onto the study and 403 courses were administered. Ninety-two patients (47 refractory and 45 sensitive) were eligible and assessable for response. Among refractory patients, there were two partial responses (PRs) and one complete response (CR), for an overall response rate of 6.4% (95% confidence interval [CI], 1.3% to 17.6%), whereas in the sensitive group, there were 11 PRs and six CRs, for an overall response rate of 37.8% (95% CI, 23.8% to 53.5%). Overall median duration of response was 7.6 months. Median survival was 5.4 months; median survival of refractory patients was 4.7 months, whereas that of sensitive patients was 6.9 months (P = .002). Median survival of responding patients was 12.5 months. Toxicity was mainly hematologic. Leukopenia, although short-lived, was universal, with grade III and IV neutropenia occurring in 28% and 46.8% of cycles, respectively. Nonhematological toxicity was mild. Fatigue/malaise was reported in 39.3% of cycles and transient elevation of liver enzymes in 17%. CONCLUSION: Topotecan has significant activity in SCLC, particularly in patients sensitive to prior chemotherapy, with predictable and manageable toxicity. The incorporation of topotecan in combination chemotherapy regimens for future treatment of SCLC is warranted.

Aged↗
PubMed1997

Preliminary results of a phase II study of paclitaxel and cisplatin in patients with non-small cell lung cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin are cytotoxic drugs active against non-small cell lung cancer (NSCLC) that possess additive cytotoxicity in animal tumors. Paclitaxel and cisplatin are active in patients with advanced NSCLC when given on a 3-weekly schedule. In an attempt to increase activity, we designed a phase II study with a biweekly schedule. Paclitaxel 110 mg/m2 was given by 3-hour intravenous infusion, followed by cisplatin 60 mg/m2 via intravenous infusion. Treatment was scheduled every 2 weeks. Of the 42 patients treated, 19 were men and 23 were women, with a median age of 54 years (range, 31 to 69 years). Four patients had stage IIIA NSCLC, 18 stage IIIB, and 20 stage IV. Median World Health Organization performance status was 1 (range, 0 to 2), and adenocarcinoma was the most common histology (52%). A median of nine cycles was administered (range, one to 24 cycles), with more than 360 cycles administered. Rates of frequency of World Health Organization grade 3 or 4 toxicities were as follows: neutropenia, 20%; thrombocytopenia, 2%; nausea/vomiting, 7% (despite prophylactic treatment with 5-HT3 receptor antagonists plus prednisolone); neurotoxicity, 2%; and nephrotoxicity, 2%. There were three septicemic episodes, no bleeding episodes, and no toxic deaths. Dose reduction was performed in 15 patients (36%), due to nephrotoxicity in 14 cases. Treatment delay was necessary in 23 patients (55%), most often due to neutropenia (nine cases). Forty patients are currently evaluable for response, with two complete and 15 partial responses (overall response rate, 43%; 95% confidence limits, 27% to 59%). Median response duration was 31 weeks (range, 9 to 85 weeks). The biweekly schedule of paclitaxel plus cisplatin has noteworthy activity in patients with NSCLC. A relatively large fraction of patients required either dose reduction and/or treatment delay, but World Health Organization grade 3 or 4 toxicity was rare, apart from the neutropenia that caused only a few septicemic episodes.

Adult↗
PubMed1997

Doxorubicin plus paclitaxel in advanced breast cancer.

The combination of bolus doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a 3-hour infusion is highly active in patients with metastatic breast cancer, but it has considerable cardiotoxicity. In this ongoing study, the potential effect of increasing the interval between administration of a short infusion of doxorubicin followed by a 3-hour infusion of paclitaxel was evaluated. Included were patients with metastatic breast cancer, who received doxorubicin 50 mg/m2 followed by paclitaxel 200 mg/m2 at intervals of 30 minutes, 4 hours, and 24 hours every 3 weeks. As of February 1997, 34 patients have been enrolled, two patients are too early to evaluate, and 13 are continuing treatment. The preliminary response rate is 69% (95% confidence interval, 50% to 84%), ranging from 60% to 80% within the three schedules. The main toxicities consisted of grade 3/4 neutropenia in 65% of all courses, with febrile neutropenia in 2%. Stomatitis and paresthesia were rare. To date, eight of 32 patients have developed abnormal left ventricular ejection fraction values and one patient has developed congestive heart failure. Our preliminary conclusions are that bolus doxorubicin followed by a 3-hour infusion of paclitaxel is highly active against metastatic breast cancer. The potential for cardiotoxicity with the regimen is reduced considerably if the maximum recommended cumulative dose of doxorubicin is reduced to 360 mg/m2 with a maximum single dose of 50 mg/m2.

Adult↗
PubMed1996

[Metastatic spinal cord compression in patients with lung cancer].

Metastatic spinal cord compression (MSCC) is a disabling complication to cancer for which the optimal treatment of choice is not settled. An analysis was performed in patients with MSCC secondary to lung cancer in order to elucidate clinical symptoms and treatment results according to regression of neurological deficits and survival. The total series consisted of 102 retrospectively evaluated patients referred for treatment, in the Eastern part of Denmark in the period 1979-1988. Patients included 40% cases with Small Cell Carcinoma (SCLC), Adeno-carcinoma (ACL) (26%), Squamous Cell Carcinoma (SQLC) (18%) and Large Cell Carcinoma (LCC) (9%). Symptoms, clinical presentations and therapeutic results are described. The outcome of treatment depended fundamentally on the patient's neurological condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory while 15% of the non-ambulatory SCLC patients regained walking ability; in non-SCLC, 95% of patients retained walking ability while 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histological types of lung cancer as to the different treatment modalities were observed, however, 82% of the patients with non-SCLC had benefit from treatment with laminectomy followed by radiotherapy compared with either laminectomy (47%) or radiotherapy (39%) alone (p = .03, Chi-square test). The group of patients treated with laminectomy followed by radiotherapy had a better survival (median value 3.5 months, range 0-132 months) than patients treated with either laminectomy (median value 1.5 months, range 0-32 months) or radiotherapy (median value 1 month, range 0-59 months) alone (p = .03, Log-Rank test). No significant difference was observed in survival between the various histological types of lung cancer (p = .18, Log-Rank test). Despite a short survival, early diagnosis and immediate treatment is crucial, since it may preserve the gait function in 97% of lung cancer patients developing malignant spinal cord compression.

Adult↗
PubMed1996

[Male breast cancer. A review].

Male breast cancer is a rare disease, making up less than 1% of all breast cancers. A review of the literature does not disclose major differences between male and female breast cancer regarding etiological, prognostic or diagnostic features. In male breast cancer endocrine therapy is more widely used, but there are otherwise no differences in the therapeutic strategies used.

Breast Neoplasms, Male↗
PubMed1996

Bioavailability of the antiemetic metopimazine given as a microenema.

The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite were measured. The bioavailability of MPZ given orally and as enemas was 22.3 and 19.5% respectively. Partial avoidance of hepatic first pass metabolism was seen with the enemas, which in contrast to suppositories, seems to represent a reliable form of rectal administration.

Administration, Oral↗
PubMed1996

Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up.

PURPOSE: The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide and vincristine as inducers of remission over three cycles; (2) compare the toxicity pattern of carboplatin and of cisplatin when given in combination regimens; and (3) compare a chemotherapeutic regimen consisting of three alternating combinations with that of regimens consisting of four alternating combinations. PATIENTS AND METHODS: From November 1985 to September 1991, 484 consecutive, previously untreated patients with SCLC, performance status 0-4, entered a three armed randomized trial with three cycles of cisplatin (arm I) or carboplatin (arm II) in combination with teniposide and vincristine alternating with three treatment blocks of cyclophosphamide, etoposide, lomustine and vincristine (block A), doxorubicin and vincristine (block B) and cisplatin, hexamethylmelamine and vindesine (block C) versus alternating treatment with block A, B and C (arm III). RESULTS: No difference in efficacy or toxicity was found between cisplatin and carboplatin at the present dosages. Induction chemotherapy with teniposide plus cisplatin or carboplatin did not result in higher complete response rates (objective response rates 63%, 72% and 65%, respectively) or in significantly greater toxicity, but overall survival was superior compared with the arm III (log-rank test, P = 0.02). The median survival difference was 7 weeks, and two year survival 15% versus 9%. The Cox regression analysis identified the arm III, poor performance status and elevated LDH as factors with statistically significant negative impact on survival. CONCLUSION: Cisplatin and carboplatin produced similar response and survival rates and similar toxicity. Induction with platinum and epipodophyllotoxins did not improve objective response rates, but significantly improved survival without increasing the toxicity.

Adult↗
PubMed1996

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic.

BACKGROUND: Paclitaxel has shown activity in metastatic breast cancer, including anthracycline-resistant breast cancer. The efficacy, toxicity and optimal scheduling of the combination of the two drugs needs to be defined. PATIENTS AND METHODS: Thirty women with advanced breast cancer who had undergone at most one prior adjuvant chemotherapy regimen, were treated at three different dose levels with doxorubicin (50, 60 and 60 mg/m2) followed 30 minutes later by paclitaxel (155, 175 and 200 mg/m2, respectively) every 3 weeks. RESULTS: The overall response rate was 83% (95% CI: 64-94), with 24% of patients achieving CR. The median response duration for complete responders was 11 months (range 4-14+) and median survival 18 months (range 3-28+). Two hundred sixty-five treatment courses were given (median 9, range 3-13) and the median cumulative dose of doxorubicin was 369 mg/m2 (range 114-550). The main toxicities were neutropenia, parestesia, nausea/vomiting, alopecia, myalgia and cardiotoxicity. Fifteen patients (50%) had reductions of left ventricular ejection fraction of below normal levels and 6 of these patients (20%) developed congestive heart failure. CONCLUSION: The combination of doxorubicin and paclitaxel is highly active, but is accompanied by the dose-limiting toxic effects of neutropenia, neuropathy and cardiotoxicity.

Adult↗
PubMed1996

Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up.

We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical progressive disease, the median positive lead time was 35 days during therapy and 76 days during follow-up. Tumor marker assessment may document that a therapy is effective and ought to be continued in spite of adverse toxic effects, and that a treatment is ineffective and should be stopped to prevent unnecessary toxicity. Marker information may also be useful in studies investigating whether early treatment during follow-up will alter the prognosis of metastatic breast cancer.

Adult↗
PubMed1996

Paclitaxel and doxorubicin, a highly active combination in the treatment of metastatic breast cancer.

The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been documented in untreated and previously treated metastatic breast cancer, including both patients with anthracycline-resistant disease and those with extensive pretreatment. Such activity has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered as either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to 72-hour infusion. Results of these completed phase I and II trials are reviewed. Also reported are two European trials that have achieved promising results. In Milan, a phase I/II trial has shown a preliminary response rate exceeding 90% in 32 chemotherapy-naive patients treated with an alternating schedule of paclitaxel given over 3 hours and intravenous bolus doxorubicin. At doses of paclitaxel 200 mg/m2 and doxorubicin 60 mg/m2, the dose-limiting toxicities were neutropenia, oral mucositis, myalgias, and peripheral neuropathy. Congestive heart failure occurred in six patients. A phase I/II study of a 30-minute doxorubicin infusion preceding a 3-hour paclitaxel infusion every 3 weeks in minimally pretreated patients also is reported. Of 29 patients evaluable for response, 17 have achieved partial responses and seven complete responses, for an overall response rate of 83% (95% confidence interval, 79% to 99%). Toxicities observed were grades 3 to 4 neutropenia and moderate paresthesias, nausea/vomiting, alopecia, myalgia, and mucositis. Cardiotoxicity also occurred, as 15 patients had a significant decrease in left ventricular ejection fraction measured by isotope cardiography. Six of these developed congestive heart failure. This effect has been observed only in studies using short infusions of both drugs, and it is now being investigated whether lowering the peak doxorubicin concentration will preclude it.

Antibiotics, Antineoplastic↗
PubMed1996

Doxorubicin and paclitaxel, a highly active combination in the treatment of metastatic breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is active against advanced breast cancer and anthracycline-resistant breast cancer. We assessed the efficacy and toxicity of doxorubicin followed by a 3-hour infusion of paclitaxel in women with advanced breast cancer. Participants could have received at most one prior adjuvant chemotherapy regimen, but no previous exposure to anthracyclines or taxanes was permitted. The patients were treated every 3 weeks with doxorubicin (50 or 60 mg/m2) followed 30 minutes later by paclitaxel (155, 175, or 200 mg/m2). After reaching the maximum cumulative doxorubicin dose, treatment could be continued with paclitaxel alone. Thirty women were included, of whom 29 were evaluable for response. The overall response rate was 83% (95% confidence interval, 64% to 94%), with 24% of patients attaining complete remission. Median response duration for complete responders was 8+ months (range, 4 to 13 months) and median time to progression was 9 months (range, 2 to 18 months). Main toxicities were neutropenia, paresthesia, nausea/vomiting, alopecia, myalgia, and cardiotoxicity. In 15 patients (50%), the left ventricular ejection fraction decreased to below normal levels; six patients (20%) developed congestive heart failure. In conclusion, the combination of doxorubicin and paclitaxel is highly active; dose-limiting toxicities are neutropenia, neuropathy, and cumulative cardiotoxicity.

Adult↗
PubMed1996

Paclitaxel and doxorubicin in metastatic breast cancer.

For the past decades the anthracyclines have been regarded as among the most active drugs for the treatment of metastatic breast cancer. However, the 5-year survival rate in patients with stage IV breast cancer continues to be below 20%, and new active drugs and drug combinations clearly must be explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines. Several studies aiming to define the optimal dose and schedule of combination paclitaxel/doxorubicin have now been completed or are ongoing. Phase I/II studies have yielded encouraging preliminary response rates but quite variable toxicity profiles depending on the schedule used. These clinical trials involving combination paclitaxel/doxorubicin are reviewed, with special emphasis on the short-infusion trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Evaluation of the optimal duration of chemotherapy in phase II trials for inoperable non-small-cell lung cancer (NSCLC).

PURPOSE: To determine the optimal duration of chemotherapy in phase II trials for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The time from start of treatment until achievement of response according to WHO criteria was determined retrospectively in 8 phase II trials. RESULTS: Response to chemotherapy consisting of 4 complete and 39 partial remissions was registered in 43 of 333 patients. The median time from treatment start to response was 54 days. On day 84 on-study, 35 of the responding patients (81%) had achieved the response. Forty-three responses (98%) had occurred by day 168 and only one patient (2%) accomplished a response after 168 days of treatment. The responses had a median duration of 151 days (range 28-1559 days). CONCLUSIONS: The data indicate that patients with NSCLC included in phase II trials who have not yet achieved a response to chemotherapy after 168 days on study have a low likelihood (2%) of a subsequent response. Hence, treatment cessation at this point should be considered for non-responding patients. Continuation of treatment from day 84 to day 168 resulted in response in only 7 patients out of the total of 43 responses noted (16%). Thus, the toxic effects of the chemotherapy in addition to the inconvenience of hospital visits renders it questionable whether it is worthwhile to continue treatment in patients with inoperable non-small-cell lung cancer beyond day 84 in the absence of response.

Adult↗
PubMed1995

Long-term survival in small-cell lung cancer: posttreatment characteristics in patients surviving 5 to 18+ years--an analysis of 1,714 consecutive patients.

PURPOSE: To describe in patients with small-cell lung cancer (SCLC) the characteristics of those who survive for > or = 5 years, to identify long-term prognostic factors, to analyze survival data of 5-year survivors, and to study 10-year survival in patients entered before 1981. PATIENTS AND METHODS: A total of 1,714 unselected patients with SCLC were treated with combination chemotherapy in nine consecutive clinical trials from 1973 to 1991. All medical records were reviewed and follow-up data obtained to analyze and compare pretreatment and posttreatment characteristics. RESULTS: Sixty patients survived longer than 5 years. Late relapses occurred in 15.0% of 5-year survivors and secondary malignancies in 20.0%. Twenty-six patients are still alive and disease-free 5 to 18 years (median, 9.5 years) from initiation of treatment. Extensive-stage disease, performance status (PS) more than 2, liver and bone marrow metastases, and elevated lactate dehydrogenase (LDH) and alkaline phosphatase levels were all negative prognostic factors. The 5-year survival rate was 3.5% (limited-stage disease, 4.8%; extensive-stage disease, 2.3%), and the 10-year survival rate was 1.8% (limited-stage disease, 2.5%; extensive-stage disease, 1.2%). CONCLUSION: Long-term survival can be achieved for both stages of SCLC, but without any change in survival rates over the last decade. Long-term survivors continuously seem to have considerable mortality due to late relapses and secondary malignancies, especially tobacco-related cancers and other tobacco-related diseases.

Alkaline Phosphatase↗