Seminars in oncology
-
Seminars in oncology · Jun 1996
Multicenter Study Clinical TrialIfosfamide-based combination chemotherapy in advanced non-small cell lung cancer: two phase I studies.
Two studies were performed to determine the maximum tolerated dose (MTD) of paclitaxel and vinorelbine, respectively, in combination with a fixed dose of ifosfamide in previously untreated patients with stage IIIB or IV non-small cell lung cancer. Response rate and survival were also assessed. Both regimens were given with mesna and granulocyte colony-stimulating factor support. ⋯ Among 42 patients treated with ifosfamide/vinorelbine, responses have been encouraging, and final analysis is pending. The dose-limiting toxicity for both regimens was neutropenia. These findings indicate that ifosfamide-containing combination chemotherapy regimens have activity in advanced non-small cell lung cancer and are well tolerated when administered with granulocyte colony-stimulating factor.
-
Seminars in oncology · Feb 1996
Multicenter Study Clinical TrialA Phase I/II study of paclitaxel and doxorubicin in the treatment of advanced breast cancer.
We designed a clinical study in which fixed doses of doxorubicin were infused by intravenous bolus 16 hours before escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, princeton, NJ) for the treatment of patients with advanced breast cancer, an interval selected to allow systemic clearance of doxorubicin before administration of paclitaxel in an outpatient setting. Courses of fixed-dose doxorubicin 50 mg/m2 by intravenous bolus and paclitaxel (doses escalated from 130 mg/m2 to 250 mg/m2 via dose escalation of 30 mg/m2) were repeated every 21 days, to a maximum of eight cycles. Maximum tolerated dose was reached if two or more of six patients at a given dose level were affected by the following events: absolute neutrophil count less than 500/microliter for > or = 7 days, absolute neutrophil count less than 100/microliter for > or = 3 days, insufficient hematopoietic recovery with absolute neutrophil count less than 1,500/microliter on day 21, febrile neutropenia, grade 4 thrombocytopenia, any World Health Organization grade 3 nonhematologic toxicity for more than 7 days. ⋯ Complete alopecia was always present. Maximum tolerated dose was not reached at paclitaxel 250 mg/m2. Ultimately, the introduction of this combination in the adjuvant setting is warranted.
-
Seminars in oncology · Dec 1995
Multicenter Study Clinical TrialSingle-agent paclitaxel by 3-hour infusion in the treatment of non-small cell lung cancer: links between p53 and K-ras gene status and chemosensitivity.
Currently available cytotoxic drugs are only moderately active in non-small cell lung cancer (NSCLC) and prolong survival only slightly. In two published trials, single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was reported to have significant activity in NSCLC, with response rates of 21% and 24%. Treatment-limiting hypersensitivity reactions, however, were noted in a phase I trial of paclitaxel given as a 3-hour infusion at doses > or = 190 mg/m2. ⋯ Granulocytopenia was generally mild. Therapy was interrupted in only two patients because of the development of grade 3 neuropathy. In our experience, paclitaxel is one of the most active cytotoxic drugs targeting NSCLC.
-
Seminars in oncology · Dec 1995
Multicenter Study Clinical TrialDocetaxel (Taxotere): an overview of first-line monotherapy.
Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has demonstrated significant activity in five phase II studies as first-line chemotherapy in the treatment of metastatic breast cancer. Overall response rates range from 55.3% to 67.7%, with responses seen at all sites of disease, including lung (40%) and liver (60%). The median duration of response was 8.3 months, and the median duration of survival was 16.4 months. ⋯ The level of activity as a single agent is comparable to that of most anthracycline and non-anthracycline combination chemotherapy regimens. Its activity does not appear to be affected by prior adjuvant chemotherapy. Further studies are ongoing to incorporate docetaxel in combination chemotherapy regimens.
-
Seminars in oncology · Oct 1994
Randomized Controlled Trial Multicenter Study Clinical TrialPaclitaxel (Taxol)/doxorubicin combinations in advanced breast cancer: the Eastern Cooperative Oncology Group experience.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to enter routine clinical practice, has aroused considerable interest due to its novel mechanism of action and its significant activity in metastatic breast cancer. Given this activity, it seemed logical to attempt to combine paclitaxel with doxorubicin, the other most active single agent in metastatic breast cancer. The Eastern Cooperative Oncology Group performed two trials investigating paclitaxel/doxorubicin combinations in patients with advanced breast cancer in an attempt to identify a tolerable dose and schedule of the combination. ⋯ This suggests that sequence of drug administration in paclitaxel-based regimens may play an important role as a determinant of toxicity and (perhaps) efficacy, a finding similar to that seen when paclitaxel and cisplatin were combined in patients with ovarian cancer. Based on this study, we identified the sequence of doxorubicin (50 mg/m2) followed by paclitaxel (150 mg/m2) to be the maximum tolerated dose. This combination is currently being compared with paclitaxel alone and doxorubicin alone in patients with advanced breast cancer in an intergroup trial led by the Eastern Cooperative Oncology Group.