Cancer treatment reports最新文献

We assessed the therapeutic efficacy and toxicity of continuous hepatic infusion of vinblastine in the treatment of breast cancer predominantly metastatic to the liver. Twenty-six patients previously treated with one or more chemotherapeutic regimens received vinblastine at a dose of 2.0 mg/m2 daily for 5 days, via percutaneously inserted intra-arterial catheters, at 3-4-week intervals. Nine of 25 evaluable patients (36%) achieved partial response and four (16%) had minor response. For responding patients, the median time to disease progression was 21 weeks (range, 12-99), with a median survival of 11 months (range, 4-29) from the beginning of hepatic arterial infusion. The toxicity of the treatment was acceptable, and drug-related effects were comparable to those seen in patients with breast cancer treated by iv continuous infusion of vinblastine at slightly lower doses. We observed two episodes of transient inappropriate antidiuretic hormone secretion. Percutaneous hepatic arterial infusion of vinblastine had significant activity in the treatment of breast cancer metastatic to the liver.

Flurbiprofen, 0.25 mg/kg, administered to mice orally once daily during 3 days prior to an iv transplantation of Lewis lung carcinoma cells, protected 50%-57% of experimental animals from the formation of lung tumor colonies. With the daily dose of 1.0 mg/kg, this effect was less pronounced. Mopidamole, twice daily 90 mg/kg orally during 3 days, did not have this effect.

Temperature-sensitive liposomes are designed to break down and release their contents preferentially at temperatures attainable by local hyperthermia. The antitumor effects of hyperthermia and anticancer drugs selectively delivered by temperature-sensitive liposomes in metastatic lymph nodes in rats were determined. Temperature-sensitive liposomes containing bleomycin (BLM) were injected sc into the dorsal surface of the right hindfoot of rats bearing AH66 ascites tumor implanted 7 days previously into a right popliteal lymph node. To break down these temperature-sensitive liposomes preferentially in the metastatic lymph nodes and to achieve the synergistic effects of local hyperthermia and BLM, we applied local hyperthermia to the right popliteal lymph node by making use of a water bath at 44 degrees C for 20 minutes. There was a significant difference in suppression of tumor growth and prolonged survival in rats receiving both temperature-sensitive liposomes containing BLM and local hyperthermia, compared with groups receiving hyperthermia alone, water solution of BLM alone, or a combination of both (P less than 0.05). The possibility that hyperthermia plus temperature-sensitive liposomes will enhance therapy for patients with metastatic lymph nodes warrants attention.

The effect of the cisplatin analogs carboplatin (CBDCA) or iproplatin (CHIP) was evaluated in patients with extensive non-small cell lung cancer. The randomized phase II design was used to achieve balance between patient groups and comparison of response rates was not a primary objective of the study. CBDCA (400 mg/m2 iv) or CHIP (270 mg/m2 iv) was administered every 4 weeks until relapse of disease. Overall, 11 of 70 patients (16%; 95% confidence interval: 7%-25%) responded to CBDCA and five of 71 patients (7%; 95% confidence interval: 1%-13%) responded to CHIP. There were two complete responses to CHIP and none to CBDCA. The most frequent severe or life-threatening toxic effects were thrombocytopenia and leukopenia. Median survival for patients receiving CBDCA was 6.5 months; for those on CHIP it was 5.0 months (P = 0.59). CBDCA is probably active in patients with non-small cell lung cancer whereas CHIP has limited activity. Further evaluation of CBDCA as part of combination chemotherapy for non-small cell lung cancer is warranted.

A number of statistical designs for phase II trials have been published. These designs are critically reviewed. A new design is also introduced. Data are presented on the response rates observed for new chemotherapeutic agents introduced by the National Cancer Institute since 1975. Based upon this material, it is recommended that two-stage designs with a target sample size of 35-50 patients and substantial probability of early termination are usually appropriate. It is also recommended that for active drugs, two to three such trials are necessary to estimate the response rate with reasonable precision. Precise estimation of phase II response rates is not always important, however. For very rare diseases or situations where several dose levels of a biologic are to be evaluated, selection designs may be most appropriate. Such designs are described. Tables are presented to facilitate the design of new agent phase II clinical trials.

To further define optimal combinations of antiemetics, high-dose metoclopramide and lorazepam (M+L) were compared with prochlorperazine and lorazepam (P+L) in a randomized, double-blind, cross-over study. Both patient and observer assessments were documented in 66 patients receiving cisplatin and noncisplatin chemotherapy. M+L significantly reduced the severity of vomiting (P = 0.01), duration of vomiting (P = 0.05), and number of vomiting episodes (P = 0.003). Comparing the severity or duration of nausea, M+L and P+L were not significantly different. M+L significantly reduced severity of vomiting (P = 0.005) and number of vomiting episodes (P = 0.03) in the cisplatin subset. The number of vomiting episodes was also reduced in the noncisplatin subset (P = 0.03). When asked to nominate a preferred regimen, 41% of patients preferred P+L, 35% preferred M+L, and 24% rated them equally. M+L was associated with significantly more anxiety and less sedation than P+L. Patient assessments produced similar results to observer assessments but gave a broader understanding of our patients' tolerance to chemotherapy. M+L is a superior regimen in controlling vomiting induced by chemotherapy.

High-dose pulse chlorambucil was given orally at a dose of 16 mg/m2 daily for 5 consecutive days each month, as reported by Cadman et al. It was used to treat 33 patients with advanced, low-grade non-Hodgkin's lymphoma. With median follow-up of 4.2+ years, 70% of the patients achieved objective response. Eleven of 24 patients with follicular small cleaved cell lymphoma (FSCL) had pathological complete response; nine of 24 with FSCL and three of seven with small lymphocytic lymphoma had partial response. Median disease-free survival was 28 months. Actuarial survival for all patients was 60% at 5 years from initiation of therapy. Treatment toxicity was minimal. Pulse chlorambucil is an effective and minimally toxic palliative therapy for advanced FSCL.

Betaseron is a genetically altered recombinant beta interferon with in vitro properties equivalent to those of native beta interferon. Nineteen patients with measurable advanced colorectal carcinoma who had no previous chemotherapy were given 30 X 10(6) IU Betaseron by iv push on Days 1-5 and 8-12 of each 28-day cycle. One of 17 evaluable patients had a complete response after nine courses of treatment which has been sustained greater than 9 months. The overall response rate was 6% (95% confidence limits, 0%-18%). Treatment was well tolerated with toxic effects consisting of fever, flu-like symptoms, nausea and vomiting, and transient mild granulocytopenia and liver function abnormalities. All toxic effects were World Health Organization (WHO) grade less than or equal to 2. No interferon neutralizing antibody activity was detected. Phase I and preclinical data support further investigation of Betaseron with dose escalation to tolerance for individual patients, as well as investigation of concomitant therapy with 5-fluorouracil, in an attempt to improve the observed response rate in colorectal cancer.