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H A Burris

Publications and source records attributed to H A Burris.

At least 37 records · Page 2Linked to original sources
PubMed2000

Phase II trial evaluating triplet chemotherapy using gemcitabine, paclitaxel, and carboplatin in the treatment of patients with advanced non-small cell lung cancer.

The purpose of this study was to evaluate the combination of gemcitabine, paclitaxel, and carboplatin in patients with advanced non-small cell lung cancer. Previously untreated patients with stage IIIB or IV non-small cell lung cancer were enrolled into this trial. Sixty-nine patients from the phase II portion and eight patients from the phase I portion were treated with gemcitabine 1,000 mg/m2 intravenously on days I and 8, paclitaxel 200 mg/m2 as a 1-hour infusion on day 1, and carboplatin at an area under the curve of 5.0 intravenously on day 1. Treatment courses were repeated every 21 days. The phase II component of the study was completed at 13 community-based practices in the Minnie Pearl Cancer Research Network. Thirty-four of 71 fully evaluable patients had an objective response (48%, two complete and 32 partial responses). Twenty-five patients (35%) were stable and 12 (17%) progressed. The median response duration was 6 months (range, 3 to 14 months) and the median survival was 9.9 months, with 1- and 2-year survival rates of 47% and 21%, respectively. The combination of gemcitabine, paclitaxel, and carboplatin has been shown to be safe and effective; thus, this three-drug regimen will be compared with a standard two-drug regimen, paclitaxel/carboplatin, in a phase III study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Docetaxel (Taxotere) in HER-2-positive patients and in combination with trastuzumab (Herceptin).

In addition to being an important indicator of poor prognosis, human epidermal growth factor receptor-2 (HER-2) status may help identify those patients in whom chemotherapy is the most appropriate choice of therapy. In several studies, including a trial of sequential neoadjuvant therapy in which certain patients received docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) following four courses of cyclophophamide 1000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2 on day one, and prednisone 40 mg by mouth for 5 days, HER-2 positivity predicted response (including pathologic response) to chemotherapy. In vitro and in vivo, docetaxel has demonstrated true synergy with the recombinant human anti-HER-2 monoclonal antibody trastuzumab (Herceptin; Genentech, San Francisco, CA). In a phase III study comparing trastuzumab alone with trastuzumab plus chemotherapy (either paclitaxel or doxorubicin plus cyclophosphamide), combining the antibody with cytotoxic drugs increased response duration, time to progression, and survival in first-line metastatic breast cancer patients. Preliminary clinical data suggest that the combination of trastuzumab with docetaxel is active and well tolerated, and pilot studies of adjuvant therapy using trastuzumab and docetaxel combinations are under way in high-risk patients.

Antibodies, Monoclonal↗
PubMed2000

Gemcitabine, paclitaxel, and carboplatin for advanced non-small-cell lung cancer.

The purpose of this study was to evaluate the combination of gemcitabine (Gemzar), paclitaxel (Taxol), and carboplatin (Paraplatin) in patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients with stage IIIB or IV NSCLC were included in this trial. A total of 69 patients from the phase II portion and 8 patients from the phase I portion were treated with gemcitabine 1,000 mg/m2 intravenously (i.v.) on days 1 and 8; paclitaxel 200 mg/m2 as a 1-hour infusion on day 1; and carboplatin at an area under the curve (AUC) dose of 5.0 i.v. on day 1. Treatment courses were repeated every 21 days. The phase II component of the study was completed at 13 community-based practices within the Minnie Pearl Cancer Research Network. Of the 71 fully evaluable patients, 34 had an objective response, for an overall response rate of 48%; 2 patients showed complete responses and 32 patients had partial responses. A total of 25 (35%) patients were stable and 12 (17%) patients progressed. The median response duration was 6 months (range 3 to 14 months), and the median survival was 9.9 months, with a 1-year survival of 47% and a 2-year survival of 21%. These results show that the combination of gemcitabine, paclitaxel, and carboplatin is safe and effective; however, randomized phase III studies are needed to prove this regimen is superior to other regimens.

Adenocarcinoma↗
PubMed1999

Phase I/II trial of paclitaxel by 1-hour infusion, carboplatin, and gemcitabine in the treatment of patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: The combination of paclitaxel and carboplatin is widely used in the treatment of patients with advanced nonsmall cell lung carcinoma. In this Phase I/II study the authors evaluated the feasibility, toxicity, and efficacy of adding a third active antineoplastic agent, gemcitabine, to the paclitaxel/carboplatin combination for the treatment of patients with advanced nonsmall cell lung carcinoma. METHODS: Patients with advanced (AJCC Stage IIIB or IV) nonsmall cell lung carcinoma previously untreated with chemotherapy were eligible for this trial. The maximum tolerated doses, determined in the Phase I trial and subsequently used in the Phase II trial, were: paclitaxel, 200 mg/m2, as a 1-hour infusion on Day 1; carboplatin, at area under the curve dose of 5.0 intravenously (i.v.), on Day 1; and gemcitabine, 1000 mg/m2 i.v., on Days 1 and 8. Treatment courses were repeated every 21 days. The Phase II study was conducted in 13 community-based practices in the Minnie Pearl Cancer Research Network; 77 patients were treated between December 1996 and September 1997. RESULTS: Thirty-four of 77 patients (44%) in the Phase II trial had major responses (partial responses, 32 patients and complete responses, 2 patients). An additional 25 patients (33%) had stable disease or minor response; only 23% of patients progressed or were removed from study at or prior to first reevaluation. The median survival was 9.4 months, with a 45% actuarial 1-year survival rate. Myelosuppression was the most common toxicity, with Grade 3/4 NCI Common Toxicity Criteria leukopenia and thrombocytopenia in 49% and 45% of patients, respectively. However, only 11 patients (14%) required hospitalization for neutropenia/ fever, and none had bleeding complications. Grade 3/4 nonhematologic toxicities included fatigue (41%), arthralgias/myalgias (26%), peripheral neuropathy (8%), nausea/emesis (6%), and hypersensitivity reactions (4%). There was one treatment-related death due to sepsis. CONCLUSIONS: This three-drug regimen is active and has acceptable toxicity in patients with advanced nonsmall cell lung carcinoma. Myelosuppression, particularly thrombocytopenia, is increased in comparison to the paclitaxel/carboplatin regimen. Fatigue also may be increased, but other nonhematologic toxicities are not altered substantially by adding gemcitabine. Although the response rate and median survival are improved modestly compared with our previous experience with paclitaxel/carboplatin, definitive conclusions regarding the efficacy of this regimen await the completion of randomized trials.

Adult↗
PubMed1999

Phase I trial of paclitaxel, carboplatin, and topotecan with or without filgrastim (granulocyte-colony stimulating factor) in the treatment of patients with advanced, refractory cancer.

BACKGROUND: Topotecan is a new antineoplastic agent with a broad spectrum of activity. The purpose of this Phase I trial was to define the maximum tolerated dose of topotecan when added to the widely used combination of paclitaxel and carboplatin. METHODS: Patients with advanced cancer that was refractory or resistant to standard treatments were treated with paclitaxel, carboplatin, and topotecan; doses were escalated in sequential cohorts of patients. After definition of the maximum tolerated dose without cytokines, granulocyte-colony stimulating factor (G-CSF) was added and further dose escalation was attempted. RESULTS: The maximum tolerated doses were: paclitaxel, 135 mg/m2, as a 1-hour intravenous (i.v.) infusion on Day 1; carboplatin, area under the curve 5.0, on Day 1; and topotecan, 0.75 mg/m2, i.v. on Days 1, 2, and 3; the regimen was repeated every 21 days. Myelosuppression, particularly thrombocytopenia, was the dose-limiting toxicity with this three-drug combination. Nonhematologic toxicity was uncommon. The addition of G-CSF did not allow substantial dose escalation because thrombocytopenia was uneffected by this agent. Eleven of 25 patients had major responses to this combination, including 8 of 14 patients with previously treated small cell lung carcinoma. CONCLUSIONS: The combination of paclitaxel, carboplatin, and topotecan is feasible, although only relatively low doses of all three drugs can be tolerated due to myelosuppression. This regimen showed a high level of activity in these patients with refractory cancer, and merits further investigation.

Adult↗
PubMed1999

A phase I evaluation of multitargeted antifolate (MTA, LY231514), administered every 21 days, utilizing the modified continual reassessment method for dose escalation.

PURPOSE: To determine toxicities, maximally tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of MTA, a novel antifolate compound which inhibits the enzymes thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFT), and dihydrofolate reductase (DHFR). METHODS: Patients with advanced solid tumors were given MTA intravenously over 10 min every 21 days. Dose escalation was based on the modified continual reassessment method (MCRM), with one patient treated at each minimally toxic dose level. Pharmacokinetic studies were performed in all patients. RESULTS: A total of 37 patients (27 males, 10 females, median age 59 years, median performance status 90%) were treated with 132 courses at nine dose levels, ranging from 50 to 700 mg/m(2). The MTD of MTA was 600 mg/m(2), with neutropenia and thrombocytopenia, and cumulative fatigue as the dose-limiting toxicities. Hematologic toxicity correlated with renal function and mild reversible renal dysfunction was observed in multiple patients. Other nonhematologic toxicities observed included mild to moderate fatigue, anorexia, nausea, diarrhea, mucositis, rash, and reversible hepatic transaminase elevations. Three patients expired due to drug-related complications. Pharmacokinetic analysis during the first course of treatment at the 600 mg/m(2) dose level demonstrated a mean harmonic half-life, maximum plasma concentration (Cpmax), clearance (CL), area under the curve (AUC), and apparent volume of distribution at steady state (Vdss) of 3.08 h, 137 microg/ml, 40.0 ml/min per m(2), 266 microg. h/ml, and 7.0 l/m(2), respectively. An average of 78% of the compound was excreted unchanged in the urine. Partial responses were achieved in two patients with advanced pancreatic cancer and in two patients with advanced colorectal cancer. Minor responses were obtained in six patients with advanced colorectal cancer. CONCLUSIONS: The MTD and dose for phase II clinical trials of MTA when administered intravenously over 10 min every 21 days was 600 mg/m(2). MTA is a promising new anticancer agent.

Adult↗
PubMed1999

Improvements in clinical benefit with vinorelbine in the treatment of hormone-refractory prostate cancer: a phase II trial.

BACKGROUND: Clinical activity is difficult to assess by traditional response endpoints in patients with advanced prostate cancer. We used clinical benefit response to assess the activity of vinorelbine (Navelbine) in patients with hormone-refractory prostate cancer. PATIENTS AND METHODS: Forty-nine men with hormone-refractory prostate cancer received vinorelbine weekly for eight weeks followed by every-other-week dosing. Clinical benefit response was defined by improvement in 1 of the following categories for at least 12 weeks and stable response or better in the other 2: pain index (analgesic consumption and pain intensity), Karnofsky performance status, and tumor status. RESULTS: Of 37 evaluable patients, 14 (39%) achieved clinical benefit for a median duration of 6 months (range 3-24 months). Toxicities consisted primarily of brief neutropenia and mild nausea. CONCLUSION: These findings indicate that vinorelbine is well tolerated in men with hormone-refractory prostate cancer and produces durable clinical benefit as defined by improvement in pain index and performance status.

Adenocarcinoma↗
PubMed1999

Phase II trial of docetaxel for cholangiocarcinoma.

The authors evaluated the activity and toxicity of docetaxel given as a 1-hour infusion every 21 days in patients with unresectable cholangiocarcinoma. Seventeen patients with cytologically or histologically confirmed cholangiocarcinoma received intravenous docetaxel over 1 hour, repeated every 21 days. The initial dose of docetaxel was 100 mg/m2, with a subsequent 25% dose reduction for patients experiencing grade 3 or 4 toxicities. Treatment was continued until disease progression or occurrence of intolerable side effects. All patients received premedication with dexamethasone 8 mg by mouth twice daily for 5 days, starting 1 day before docetaxel infusion. Sixteen of the 17 patients were assessable for response and toxicity; one patient was removed from the trial for intercurrent illness. Thirty-eight cycles of docetaxel were delivered (median, two cycles). No complete or partial responses were noted. Fourteen patients had progressive disease, one patient had stable disease, and one patient died of septic shock shortly after starting treatment. Granulocytopenia was the dose-limiting toxicity. Thirteen patients had grade 4 granulocytopenia, 11 of whom required antibiotics for neutropenic fever. Granulocytopenia was the only grade 4 toxicity observed. Grade 3 toxicities included stomatitis, anemia, fatigue, vomiting, and hypotension. Grade 1 or 2 toxicities included alopecia, diarrhea, peripheral edema, myalgias, and anorexia. Administered on this dose and schedule, docetaxel lacked activity in patients with cholangiocarcinoma. The toxicity profile, including dose-limiting granulocytopenia, has been previously described in patients receiving docetaxel.

Adult↗
PubMed1999

Phase I and pharmacokinetic study of the oral fluoropyrimidine capecitabine in combination with paclitaxel in patients with advanced solid malignancies.

PURPOSE: To evaluate the feasibility of administering the oral fluoropyrimidine capecitabine in combination with paclitaxel, to characterize the principal toxicities of the combination, to recommend doses for subsequent disease-directed studies, and to determine whether significant pharmacokinetic interactions occur between these agents when combined. PATIENTS AND METHODS: Sixty-six courses of capecitabine and paclitaxel were administered to 17 patients in a two-stage dose-escalation study. Paclitaxel was administered as a 3-hour intravenous (IV) infusion every 3 weeks, and capecitabine was administered continuously as two divided daily doses. During stage I, capecitabine was escalated to a target dose of 1,657 mg/m(2)/d, whereas the paclitaxel dose was fixed at 135 mg/m(2). In stage II, paclitaxel was increased to a target dose of 175 mg/m(2), and the capecitabine dose was the maximum established in stage I. Pharmacokinetics were characterized for each drug when given alone and concurrently. RESULTS: Myelosuppression, predominately neutropenia, was the principal dose-limiting toxicity (DLT). Other toxicities included hand-foot syndrome, diarrhea, hyperbilirubinemia, skin rash, myalgia, and arthralgia. Two patients treated with capecitabine 1,657 mg/m(2)/d and paclitaxel 175 mg/m(2) developed DLTs, whereas none of six patients treated with capecitabine 1,331 mg/m(2)/d and paclitaxel 175 mg/m(2) developed DLTs during course 1. Pharmacokinetic studies indicated that capecitabine and paclitaxel did not affect the pharmacokinetic behavior of each other. No major antitumor responses were noted. CONCLUSION: Recommended combination doses of continuous capecitabine and paclitaxel are capecitabine 1,331 mg/m(2)/d and paclitaxel 175 mg/m(2)/d IV every 3 weeks. Favorable preclinical mechanistic interactions between capecitabine and paclitaxel, as well as an acceptable toxicity profile without clinically relevant pharmacokinetic interactions, support the performance of disease-directed evaluations of this combination.

Administration, Oral↗
PubMed1999

A phase I and pharmacokinetic study of losoxantrone and paclitaxel in patients with advanced solid tumors.

A Phase I and pharmacological study was performed to evaluate the feasibility, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics of the anthrapyrazole losoxantrone in combination with paclitaxel in adult patients with advanced solid malignancies. Losoxantrone was administered as a 10-min infusion in combination with paclitaxel on either a 24- or 3-h schedule. The starting dose level was 40 mg/m2 losoxantrone and 135 mg/m2 paclitaxel (as a 24- or 3-h i.v. infusion) without granulocyte colony-stimulating factor (G-CSF). Administration of these agents at the starting dose level and dose escalation was feasible only with G-CSF support. The following dose levels (losoxantrone/paclitaxel, in mg/m2) of losoxantrone and paclitaxel as a 3-h infusion were also evaluated: 50/135, 50/175, 50/200, 50/225, and 60/225. The sequence-dependent toxicological and pharmacological effects of losoxantrone and paclitaxel on the 24- and 3-h schedules of paclitaxel were also assessed. The MTD was defined as the dose at which >50% of the patients experienced DLT during the first two courses of therapy. DLTs, mainly myelosuppression, occurring during the first course of therapy were noted in four of six and five of eight patients treated with 40 mg/m2 losoxantrone and 135 mg/m2 paclitaxel over 24 and 3 h, respectively, without G-CSF. DLTs during the first two courses of therapy were observed in one of six patients at the 50/175 (losoxantrone/paclitaxel) mg/m2 dose level, two of four patients at the 50/200 mg/m2 dose level, one of four patients at the 50/225 mg/m2 dose level, and two of five patients at the 60/225 mg/m2 dose level. The degree of thrombocytopenia was worse, albeit not statistically significant, when 24-h paclitaxel preceded losoxantrone, with a mean percentage decrement in platelet count during course 1 of 80.7%, compared to 43.8% with the reverse sequence (P = 0.19). Losoxantrone clearance was not significantly altered by the sequence or schedule of paclitaxel. Cardiac toxicity was observed; however, it was not related to total cumulative dose of losoxantrone. An unacceptably high rate of DLTs at the first dose level of 40 mg/m2 losoxantrone and 135 mg/m2 paclitaxel administered as either a 24- or 3-h i.v. infusion precluded dose escalation without G-CSF support. The addition of G-CSF to the regimen permitted further dose escalation without reaching the MTD. Losoxantrone at 50 mg/m2 followed by paclitaxel (3-h i.v. infusion) at 175 mg/m2 with G-CSF support is recommended for further clinical trials.

Adult↗
PubMed1999

Single-agent docetaxel (Taxotere) in randomized phase III trials.

Until recently, there has been no standard treatment for patients with metastatic breast cancer who have failed an anthracycline-containing regimen, and no definitive phase III trials had been conducted in this setting. The results of three randomized phase III clinical trials of single-agent docetaxel (Taxotere, Rhône-Poulenc Rorer, Collegeville, PA) 100 mg/m2 every 3 weeks in comparison to combination chemotherapy regimens in patients with metastatic breast cancer pretreated with an anthracycline-based chemotherapy regimen are reviewed and reported. An overall response rate of between 30% and 42% was reported for single-agent docetaxel, which was higher in comparison to response rates attained with the combination chemotherapy regimens in all three trials. Noteworthy were findings of a significantly improved overall survival for docetaxel-treated patients in one of the comparative trials. These results firmly establish docetaxel as preferred therapy over combination chemotherapy regimens with mitomycin C plus vinblastine, methotrexate plus 5-fluorouracil, or 5-fluorouracil plus vinorelbine in the therapy of anthracycline-resistant and/or anthracycline-pretreated metastatic breast cancer patients. The results document the continued high level of docetaxel antitumor activity in previously anthracycline-exposed patients initially reported in phase II trials and confirm a substantial lack of anthracycline cross-resistance. The higher response rate of single-agent docetaxel versus single-agent doxorubicin as demonstrated in a fourth randomized phase III trial gives credence to the presumption that the combination of these two agents may provide a highly effective chemotherapy regimen in the management of breast cancer patients.

Anthracyclines↗
PubMed1999

Weekly administration of docetaxel (Taxotere): summary of clinical data.

Docetaxel (Taxotere; Rhône-Poulence Rorer, Antony, France) is a highly efficacious antineoplastic agent; however, its administration every 3 weeks produces substantial myelosuppression. Based on recent observations that the administration of paclitaxel on a weekly schedule minimizes myelosuppression, investigation of weekly docetaxel has been initiated. A recently completed phase I study of weekly docetaxel demonstrates markedly decreased myelosuppression with this schedule. The maximum tolerated dose was 43 mg/m2/wk; with this dose, myelosuppression was mild and the dose-limiting toxicity was fatigue/asthenia. Other nonhematologic toxicities were uncommon when doses of less than 40 mg/m2/wk were administered. Edema was not observed, in spite of an abbreviated dexamethasone schedule (8 mg every 12 hours for three doses, beginning 12 hours before docetaxel). A 50% response rate using docetaxel 35 to 40 mg/m2/wk has been achieved in patients with metastatic breast cancer. When used concurrently with radiation therapy, weekly scheduling allowed a maximization of docetaxel dosing, with the maximum tolerated dose being 20 mg/m2/wk. It is likely that this novel schedule of docetaxel will allow the drug to be used with decreased toxicity and will facilitate its incorporation into active combination regimens. Further investigation of this novel schedule of administration is warranted.

Antineoplastic Agents, Phytogenic↗
PubMed1999

The evolving role of oral topotecan.

Pharmacokinetic characteristics, efficacy, and safety of oral topotecan, a topoisomerase-I inhibitor, were evaluated in phase I and phase II clinical trials. Results of the pharmacokinetic analyses showed that orally administered topotecan has a lower peak plasma concentration (Cmax) and longer mean residence time than intravenously administered drug. Preliminary data suggest that the oral formulation has efficacy similar to that of the intravenous (IV) formulation in patients with recurrent or refractory ovarian and small-cell lung cancer. The type and degree of toxicity appeared to be related to the dosing schedule (number of days of consecutive treatment), but overall, oral topotecan appeared to be associated with less hematologic toxicity than the IV formulation.

Administration, Oral↗
PubMed1998

Phase I trial of paclitaxel and gemcitabine administered every two weeks in patients with refractory solid tumors.

PURPOSE: Paclitaxel and gemcitabine possess broad spectra of clinical activity, distinct mechanisms of cytotoxicity, and are differentially affected by mutations in cell-cycle regulatory proteins, such as bcl-2. This phase I trial was designed to identify the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of paclitaxel and gemcitabine when both drugs were given together on a once-every-two-week schedule in patients with solid tumors. PATIENTS AND METHODS: A total of 37 patients were treated at nine different dose levels ranging from paclitaxel 75-175 mg/m2 administered over three hours followed by gemcitabinc 1500-3500 mg/m2 administered over 30-60 minutes. Both drugs were administered on day 1 of a 14-day cycle. Dose escalation was performed in a stepwise manner in which the dose of one drug was escalated while the dose of the other drug was kept constant. RESULTS: Dose limiting toxicity (DLT) was observed at dose level 9: paclitaxel 175 mg/m2 and gemcitabine 3500 mg/m2 in the form of grade 4 neutropenia lasting for > or = 5 days (one patient) and grade 3 elevation of alanine aminotransferase (AST/SGPT) (one patient). An analysis of delivered dose intensity (DI) over the first three cycles revealed that higher dosages of both drugs were delivered at dose level 7, paclitaxel 150 mg/m2 and gemcitabine 3000 mg/m2 dose level, than at the MTD, dose level 8, paclitaxel 150 mg/m2 and gemcitabine 3500 mg/m2. Partial responses were confirmed in two patients with transitional cell carcinoma (one of the bladder, one of the renal pelvis) and in one patient with adenocarcinoma of unknown primary. CONCLUSIONS: Paclitaxel and gemcitabine is a promising drug combination that can be administered safely and repetitively on an every-other-week schedule. Using this drug administration schedule, the recommended phase II dose is paclitaxel 150 mg/m2 and gemcitabine 3000 mg/m2.

Adult↗
PubMed1998

Pharmacokinetic and phase I studies of brequinar (DUP 785; NSC 368390) in combination with cisplatin in patients with advanced malignancies.

Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, patients were initially treated with weekly brequinar, in combination with an every-three-week administration of cisplatin. Due to toxicity, the schedule was modified to a 28-day cycle with brequinar given on days 1, 8, 15, and cisplatin on day 1. A total of 24 patients (16 male, 8 female; median age 57; median performance status 1) received 69 courses of therapy. Six dose levels were explored, with cisplatin/ brequinar doses, respectively, of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2. The serum concentration versus time curves for brequinar were biphasic. A comparison of the pharmacokinetic results after the first and third doses of brequinar indicate that the presence of 50, 60, and 75 mg/m2cisplatin did not change the protein binding and the pharmacokinetics of brequinar in any of the three brequinar-dose groups. Total cisplatin plasma pharmacokinetic followed a triphasic-shape curve and unbound cisplatin decayed at a very rapid rate. Since pharmacokinetic parameters for total cisplatin in this study were similar to those reported in the literature, the presence of brequinar is unlikely to alter the pharmacokinetics of cisplatin. Main dose-limiting toxicities included myelosuppression (including neutropenia and thrombocytopenia) and mucositis. Cisplatin/brequinar doses of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2, were associated with dose limiting toxicity in 0/3, 1/3, 1/3, 1/3, 2/4, 2/5, and 4/6 patients, respectively. This study shows that co-administration of brequinar and cisplatin does not affect the pharmacokinetic properties of either drug and that the MTDs of cisplatin/brequinar combinations are 60/860 mg/m2 or 75/650 mg/m2. From this study, we conclude that full dose of 75 mg/m2 cisplatin (day 1) can be administered with 650 mg/m2 brequinar (days 1, 8 and 15) without significant modifications of individual drug pharmacokinetic parameters.

Adolescent↗
PubMed1998

A phase I trial of vinorelbine in combination with mitoxantrone in patients with refractory solid tumors.

Vinorelbine (Navelbine) is a unique semi-synthetic vinca-alkaloid with a favorable safety profile that has demonstrated significant antitumor activity in patients with non-small cell lung cancer, advanced breast cancer, advanced ovarian cancer and Hodgkin's disease. The most common dose-limiting toxicity is neutropenia, while other reported toxicities are minimal. Mitoxantrone (Novantrone) is an anthracene derivative that has demonstrated antitumor activity in patients with breast cancer, ovarian cancer, acute leukemia, and lymphoma. Mitoxantrone also has a very favorable toxicity profile with significantly less nausea and vomiting, alopecia, and stomatitis as compared with anthracyclines. The dose-limiting toxicity for mitoxantrone is leukopenia. The study was designed to determine the safety and maximally tolerated dose of IV vinorelbine used in combination with a fixed dose of mitoxantrone for the treatment of patients with refractory solid tumors. Vinorelbine was administered on days 1 and 8 of the treatment regimen as a short IV infusion. The starting dose was 15 mg/m2. Mitoxantrone was administered as a 20-min infusion on day 1 only at a fixed dose of 10 mg/m2. Seventeen patients with solid malignancies were entered in the study. For personal reasons, one patient decided to discontinue the treatment after day 1 of cycle 1. Therefore, 16 patients were evaluable for toxicity. The main toxicity was myelosuppression which was dose-limiting and resulted in dose reductions and delays. The use of G-CSF had a minimal overall impact on this regimen. Stable disease was observed in three cases. In patients previously treated with chemotherapy, the maximally tolerated dose was defined as vinorelbine 20 mg/m2 on days 1 and 8 and mitoxantrone 10 mg/m2 on day 1 without growth factor support. These doses can be recommended for phase II study of the regimen as salvage treatment.

Adult↗
PubMed1998

Intratumoral cisplatin/epinephrine-injectable gel as a palliative treatment for accessible solid tumors: a multicenter pilot study.

Intratumoral injections of cisplatin/epinephrine-injectable gel were administered weekly for 4 weeks in 45 patients with malignant tumors of various histologic types. Tumors were located on the skin and subcutaneous tissue primarily of the head, neck, and trunk, and on the tongue, oral pharynx, and esophagus. Patients were not candidates for surgery, radiation, or systemic chemotherapy. Each of the treated tumors (n = 82) was evaluated 2, 4, 8, and 12 weeks after the final injection. The initial dose of cisplatin was 1 mg/cm3 tumor volume, with escalation to 6 mg/cm3 allowed, depending on observed toxicities. The mean cumulative dose per patient for the four treatments ranged from 0.56 to 380 mg cisplatin. No dose-limiting cisplatin-related toxicities, such as nephrotoxicity, neurotoxicity, or ototoxicity, were observed. The overall objective tumor response rate was 50% (41 of 82), with 40% (33 of 82) complete responses and a median response duration of 160 days. Complete responses for adenocarcinoma and squamous cell carcinoma were 58% (21 of 36) and 38% (12 of 32), respectively. These results justified further clinical trials to evaluate the role of local chemotherapy with intratumoral cisplatin/epinephrine-injectable gel in the palliative treatment of patients with selected accessible solid tumors.

Adenocarcinoma↗