ABSTRACT
The preparation of zwitterionic latex particles is reported by using a mixed anionic and cationic initiator system without requiring surface-active agents. Isoelectric points were found from microelectrophoresis experiments and were in the pH range of 3.5-5. Close to the isoelectric point, the latices coagulated as expected, and good stability was achieved outside this narrow range. This range of stability was in good agreement with predictions from current theory. Redispersion after coagulation was found to be difficult as was expected for a hydrophobic colloid. The electrokinetic behavior did not result in the maximum in zeta potential at an electrolyte concentration of 1 mM unlike the situation for other hydrophobic polystyrene latex particles, and hence these systems may be even better models for other colloidal studies.
ABSTRACT
BACKGROUND: The combination of oral estramustine and oral etoposide has generated response rates of 40-50% in patients with hormone refractory prostate cancer in single institution trials. This study tested this regimen in a multi-institutional setting. METHODS: Fifty-five patients were accrued over a period of 4 months between 1 March 1996 and 1 July 1996. Two patients were not analyzable and two patients were ineligible. They were given an oral regimen consisting of estramustine 15 mg/kg/day (capped at 1120 mg per day) and etoposide 50 mg/M(2)/day, days 1-21 every 28 days. Patients received a median of two cycles of therapy. RESULTS: Toxicities included 11 patients (20%) with grades 3 or 4 granulocytopenia, 5 patients (10%) with grades 3 or 4 edema, and 3 patients (6%) with a thrombotic event. There were two treatment-related deaths, one as a result of anemia and the other as a result of a myocardial infarction. Of the 32 men who received at least 2 cycles of therapy, 7 men (22%) demonstrated a partial response to this regimen as measured by prostate-specific antigen (PSA) criteria of a 50% decline from pretreatment values. CONCLUSIONS: This trial demonstrates the toxicity of estramustine delivered in high dose. It also illustrates the difficulty of conducting phase II trials in prostate cancer in the cooperative group setting where the experience and comfort level of oncologists with new agents is less than that of the physicians at the institution where the therapy was developed. As the activity of this regimen with low-dose estramustine is defined, further multi-institutional studies may be warranted.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prostatic Neoplasms/drug therapy , Administration, Oral , Aged , Aged, 80 and over , Androgens/metabolism , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Administration Schedule , Estramustine/administration & dosage , Etoposide/administration & dosage , Humans , Male , Middle Aged , Nausea/chemically induced , Prostate-Specific Antigen/blood , Prostatic Neoplasms/immunology , Prostatic Neoplasms/metabolism , Treatment Outcome , Venous Thrombosis/chemically inducedABSTRACT
PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P =.006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0. 91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Etoposide/administration & dosage , Lung Neoplasms/drug therapy , Canada , Carcinoma, Small Cell/mortality , Carcinoma, Small Cell/pathology , Carcinoma, Small Cell/radiotherapy , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Etoposide/adverse effects , Etoposide/therapeutic use , Female , Humans , Logistic Models , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Male , Middle Aged , Prognosis , Survival Analysis , United States , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
PURPOSE: Several agents have been evaluated for their effect as biochemical modulators of fluorouracil (5-FU) in the treatment of metastatic colorectal carcinoma. In this study, we used folinic acid (FA), N-phosphonacetyl-L-aspartic acid (PALA), and recombinant interferon alfa-2a (IFNalpha-2a) in a sequential order to assess the efficacy of this approach in patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Forty-four patients with metastatic colorectal carcinoma were enrolled onto the study. The treatment course consisted of three cycles: (cycle 1) FA 20 mg/m(2) followed by 5-FU 425 mg/m(2) on days 1 to 5; (cycle 2) PALA 250 mg/m(2) on days 29, 36, 43, and 50 and 5-FU 2,600 mg/m(2) as a 24-hour infusion on days 30, 37, 44, and 51; and (cycle 3) IFNalpha-2a 9 million units (MU) three times a week for 5 weeks beginning on day 57, with a continuous infusion of 5-FU 750 mg/m(2) on days 57 to 61, and then weekly bolus of 5-FU 750 mg/m(2)/wk on days 71, 78, and 85. Response was determined after cycle 3. RESULTS: All patients had a Zubrod performance status >/= 2, measurable disease, and had received no prior chemotherapy for their metastatic disease. A total of 212 cycles were given. Thirty-six patients were assessable for response. No complete responses were seen. Seven patients had a partial response, eight had stable disease, and 15 had progressive disease. The median duration of response was 25 weeks, and the median survival was 53 weeks. Grade 3 and 4 toxic effects included granulocytopenia, stomatitis, diarrhea, rash, nausea, and fatigue. CONCLUSION: This trial provided no evidence that sequential biochemical modulation of 5-FU in patients with metastatic colorectal carcinoma had any therapeutic advantage over conventional treatment regimens of 5-FU plus FA.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/administration & dosage , Aspartic Acid/analogs & derivatives , Colorectal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Immunologic Factors/administration & dosage , Interferon-alpha/administration & dosage , Leucovorin/administration & dosage , Phosphonoacetic Acid/analogs & derivatives , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/pharmacokinetics , Aspartic Acid/administration & dosage , Colorectal Neoplasms/pathology , Combined Modality Therapy , Drug Administration Schedule , Drug Interactions , Female , Fluorouracil/pharmacokinetics , Humans , Infusions, Intravenous , Injections, Intravenous , Injections, Subcutaneous , Male , Middle Aged , Phosphonoacetic Acid/administration & dosage , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: This phase II multi-institutional trial of the Southwest Oncology Group was designed to evaluate the efficacy and toxicity of docetaxel in chemotherapy-naive patients with extensive-stage small cell lung cancer. PATIENTS AND METHODS: Forty-seven patients with extensive-stage small cell lung cancer were entered onto the study. Treatment consisted of docetaxel, 100 mg/m2, as a 1-hour intravenous infusion repeated every 21 days, with protocol-specified dose reductions for toxicity. RESULTS: Forty-three patients were eligible. A total of 158 cycles of docetaxel were administered (median, three cycles; range, one to nine). Ten patients (23%) (95% confidence interval, 12% to 39%) achieved partial responses. The median progression-free and overall survivals were 3 and 9 months, respectively. Therapy was generally well tolerated. Grade 4 neutropenia occurred in 58% of patients. Febrile neutropenia developed in five patients (12%), and infection was documented in 14% of patients. There was one treatment-related death caused by pneumonia in a patient who had developed bilateral pneumothoraces. Other toxicities (grade 3/4) included malaise, fatigue, and lethargy (21%); nausea (19%); stomatitis (14%); edema (9%); and sensory neuropathy (9%). DISCUSSION: Docetaxel, at a dose of 100 mg/m2, is an active agent in the treatment of small cell lung cancer. Reversible neutropenia is the most common toxicity associated with this treatment. The overall survival (9 months) with this agent is comparable to that reported with other new chemotherapeutic agents in small cell lung cancer and warrants additional evaluation of docetaxel in combination therapy.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Small Cell/drug therapy , Lung Neoplasms/drug therapy , Paclitaxel/analogs & derivatives , Taxoids , Adult , Aged , Antineoplastic Agents, Phytogenic/adverse effects , Docetaxel , Drug Administration Schedule , Female , Humans , Injections, Intravenous , Male , Middle Aged , Paclitaxel/adverse effects , Paclitaxel/therapeutic useABSTRACT
Malignant melanoma is increasing in incidence in this country. Metastatic disease generally responds poorly to most chemotherapy drugs. Immunologic and biologic agents have shown some activity in this disease. Interleukin 4 (IL-4) is a cytokine produced by activated T-lymphocytes with pluripotent activities including growth inhibition of various tumor cell lines in vitro and immune- mediated tumor growth inhibition in in vivo animal tumor models. In this phase II trial, patients with advanced malignant melanoma with no prior systemic therapy for metastatic disease and Southwest Oncology Group performance status 0-1 were treated with recombinant human IL-4 at a dose of 5 micrograms/kg/day by daily subcutaneous injection days 1-28 followed by a 7-day rest period, after which the cycle was repeated. Thirty-six patients were registered to this study. Two patients were ineligible by study criteria. Among the 34 eligible patients, there was 1 complete response, 0 partial responses, 2 stable/no responses, 27 increasing disease/progression, 1 early death, and 3 patients whose assessment was inadequate to determine response. The overall estimated response rate was 3% (1 of 34) with a 95% confidence interval 0.1-15%. The duration of the complete response is 421+ days. Thirty-one of the 34 eligible patients have died. The estimated median survival is 6 months (95% confidence interval 4-9 months). The most common toxicities were elevated liver function tests, nausea/vomiting/diarrhea, malaise/fatigue, edema, headache, myalgias/arthralgias, and fever/chills. Despite promising preclinical growth inhibitory and immunomodulatory effects, IL-4 in this dose and schedule showed only low antitumor activity. Alternative methods and routes of administration or combinations of IL-4 with other cytokines might produce greater antitumor effects.
Subject(s)
Interleukin-4/therapeutic use , Melanoma/drug therapy , Adult , Aged , Female , Humans , Incidence , Interleukin-4/adverse effects , Male , Melanoma/epidemiology , Melanoma/pathology , Middle Aged , Neoplasm Invasiveness , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Southwestern United States/epidemiology , Survival Rate , Treatment OutcomeABSTRACT
PURPOSE: The primary objectives of the study were to evaluate the efficacy and safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy plus concurrent chest/brain irradiation induction, followed by CAV consolidation, in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD) within a cooperative group setting. METHODS AND MATERIALS: Fifty-six eligible patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m2 i.v. (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m2 (days 1-14, 29-42, and 57-70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT) was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an AP:PA arrangement, to begin concomitantly with induction chemotherapy. Prophylactic cranial irradiation (PCI) was started on day 15 of induction therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21-day cycles of consolidation cyclophosphamide 750 mg/m2 i.v., doxorubicin 50 mg/m2 i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on day 106 or week 16, from the start of induction therapy. RESULTS: Among 56 eligible patients, 93% had SWOG performance status 0-1. All had adequate organ function and had not received prior therapy. The overall confirmed response rate was 46%, including 16% complete responders and 30% partial responders. After a minimum follow-up duration of 17 months, the Kaplan-Meier median progression-free (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven patients (20%) discontinued secondary to toxicity and two patients died from treatment. The major toxicity was hematologic. The two deaths were secondary to infection. Of the nonhematologic toxicities, there were 10 cases of pulmonary fibrosis (including one Grade 3) and six cases of pneumonitis (including one Grade 3). CONCLUSION: Concomitant chemoradiation with oral etoposide as part of a platinum-based chemotherapy and TRT induction regimen is toxic. The CR rate is not better than our prior best group-wide experience. The progression-free and overall survival are similar to published trials utilizing short-course i.v. etoposide. As in chemotherapy for extensive-stage SCLC, there is no apparent advantage to prolonged exposure to etoposide, and toxicity resulted in an inferior therapeutic index compared to programs with shortened exposure.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/radiotherapy , Cranial Irradiation , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Administration, Oral , Adult , Aged , Carcinoma, Small Cell/mortality , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Survival Analysis , Vincristine/administration & dosageABSTRACT
BACKGROUND: The combined use of cisplatin and carboplatin chemotherapy offers a unique means of platinum dose intensification. Response rates using either of these agents in combination with etoposide are comparable. In a Phase II trial, the authors investigated the combination of cisplatin and carboplatin with etoposide for the treatment of patients with advanced nonsmall cell lung carcinoma. METHODS: Eligible patients were chemotherapy naive and had histologically confirmed, evaluable, or measurable selected Stage IIIB and Stage IV nonsmall cell lung carcinoma. Based upon the results of an earlier Phase I and II pilot study, patients received carboplatin, 225 mg/m2, on Day 1; cisplatin, 50 mg/m2, on Days 2 and 3; and etoposide, 75 mg/m2, on Days 1, 2, and 3 every-4-weeks. RESULTS: Eighty-three patients (75 eligible patients) received chemotherapy with cisplatin, carboplatin, and etoposide. Two patients refused therapy after registration and were not analyzable. Thirty-six of the remaining 75 patients had Grade 4 toxicities, mostly hematologic, and 6 patients died of toxicity. The confirmed response rate was 24% (95% confidence interval, 15-35%). Median progression-free survival was 4 months and the median survival was 8 months. CONCLUSIONS: Combination cisplatin, carboplatin, and etoposide chemotherapy appears to be no better than cisplatin/etoposide or carboplatin/etoposide for the treatment of patients with nonsmall cell lung carcinoma. The toxicity of this regimen may be higher, and therefore it cannot be recommended for general use.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/secondary , Cisplatin/administration & dosage , Confidence Intervals , Etoposide/administration & dosage , Female , Hematologic Diseases/chemically induced , Humans , Kidney Diseases/chemically induced , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Survival RateABSTRACT
BACKGROUND: Renal cell carcinoma is a common neoplasm that is often refractory to treatment. It is occasionally responsive to immunomodulating agents including interferon-alpha, which enhances the effects of 5-fluorouracil upon cells. Combinations of these two drugs have been most frequently tested in patients with gastrointestinal cancers, with some promising results. Because interferon-alpha has activity for renal cell carcinoma, a trial of this combination in patients with this malignancy was undertaken. METHODS: The Southwest Oncology Group performed a Phase II clinical trial of the combination of 5-fluorouracil and interferon-alpha for recurrent or metastatic renal cell carcinoma. Eligibility criteria included no prior treatment with medications for cancer, a performance status of 2 or better, and bidimensionally measurable disease. The regimen studied consisted of 5-fluorouracil, 750 mg/M2/day, by continuous intravenous infusion on Days 1-5, and interferon-alpha-2b (Intron A), 5 x 10(6)U/M2/day, subcutaneously on Days 1, 3, and 5, repeated every 21 days. RESULTS: Forty eligible patients were treated; twenty of the 40 underwent a nephrectomy. The regimen was tolerable: 3 patients had Grade 4, and 17 had Grade 3 toxicity. There were 5 partial responses (13% with 95% confidence limits of 4-27%). Median progression free survival for all 40 patients was 4 months and median overall survival was 15 months from the time of registration. CONCLUSIONS: The combination of 5-fluorouracil and interferon-alpha given by this schedule, although tolerable and occasionally yielding responses, is not an improvement over existing therapies.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Agranulocytosis/chemically induced , Anemia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Confidence Intervals , Female , Fluorouracil/administration & dosage , Gastritis/chemically induced , Humans , Interferon-alpha/administration & dosage , Kidney Neoplasms/mortality , Male , Middle Aged , Survival RateABSTRACT
Based on the reports of substantial improvement in the response rate w ith the addition of tamoxifen to a multiagent chemotherapy regimen for metastatic melanoma, Southwest Oncology Group (SWOG)-8921 was initiated. A prior regimen (SWOG-8804) of dacarbazine (DTIC) 750 mg/m(2) i.v. day 1 and cisplatin 100 mg/m(2) day 1 repeated every 3 weeks produced a 13% response rate in patients with metastatic melanoma without brain metastasis. SWOG-8921 using identical chemotherapy and schedule added tamoxifen 10 mg twice daily. There were 55 eligible patients registered, median age 52, with 37 men and 18 women. Fifty (91%) patients had evidence of visceral metastasis at registration. There were 10 responders (2 complete and 8 partial responses) for an 18% response rate (95% CI, 9-31%). The response rate in women was 28% (95% CI, 10-53%; in men, 14% (95% CI, 5-29%). Tamoxifen has produced a small increase in the response rate when added to the present combination and schedule of chemotherapy. Further Phase III trials will be necessary to assess whether there is a statistical advantage to the use of tamoxifen when combined with chemotherapy and whether there are statistical differences between men and women.
Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Dacarbazine/administration & dosage , Estrogen Antagonists/administration & dosage , Melanoma/drug therapy , Melanoma/secondary , Tamoxifen/administration & dosage , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/adverse effects , Dacarbazine/adverse effects , Drug Administration Schedule , Estrogen Antagonists/adverse effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Remission Induction , Sex Factors , Tamoxifen/adverse effectsABSTRACT
BACKGROUND: Fazarabine is a novel nucleoside with broad spectrum pre-clinical activity and was chosen for study in patients with incurable non-small cell carcinoma of the lung. The expenses associated with investigational treatment have been assumed to be more than what would occur with conventional therapy, however, data are limited. METHODS: Twenty-three patients with metastatic non-small cell lung cancer were treated with fazarabine. Fazarabine was administered as a 72 hour continuous infusion at 2.0 mg/M2/hour. A cost analysis of treatment was calculated for patients treated in Springfield, MO. RESULTS: There were no responses (0%, 95% confidence interval = 0-15%) and median survival was 8 months. An analysis of the cost of treatment in the 4 patients treated in Springfield, MO, was compared to the costs of treatment with 4 cycles of cisplatinum and etoposide. There were no significant differences in costs for patients treated with the investigational agent as compared with conventional chemotherapy. CONCLUSIONS: Fazarabine has no demonstrable activity in patients with metastatic non-small cell carcinoma of the lung. Treatment with this agent in an investigational setting was no more expensive than treatment with conventional chemotherapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Azacitidine/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents/economics , Azacitidine/economics , Azacitidine/therapeutic use , Cost-Benefit Analysis , Dose-Response Relationship, Drug , Female , Humans , Male , Middle AgedABSTRACT
Piroxantrone is an anthrapyrazole compound undergoing phase II testing in a variety of diseases. The anthrapyrazoles are a series of compounds synthesized with the intent of maintaining the broad antitumor activity of anthracyclines, but with lessened cardiac toxicity. The Southwest Oncology Group (SWOG) conducted a phase II trial of piroxantrone in advanced soft tissue sarcoma. Treatment consisted of piroxantrone 150 mg/M2 administered intravenously over 1 hour every 21 days. Twenty-five eligible patients were registered to the trial. Twenty-three patients received treatment and are fully evaluable for response and toxicity. Two partial responses were seen for an overall response rate of 9% (95% confidence limit 1%-28%). Abnormal cardiac ejection fraction occurred in five patients, and fatal congestive heart failure developed in one patient on study. Toxicities other than cardiac were tolerable. Based on the observed response rate and cardiac toxicity, further trials of piroxantrone in the treatment of soft tissue sarcoma do not appear warranted.
Subject(s)
Anthraquinones/therapeutic use , Antineoplastic Agents/therapeutic use , Pyrazoles/therapeutic use , Sarcoma/drug therapy , Adult , Aged , Anthraquinones/administration & dosage , Anthraquinones/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Sarcoma/secondaryABSTRACT
The objective of this trial was to determine the efficacy of echinomycin (1.2 mg/m2) administered on a weekly times four schedule in the treatment of patients with recurrent or progressive central nervous malignancies despite adequate radiotherapy. Thirty-five patients were registered on study. The majority of patients (20) had glioblastoma multiforme. Ten had anaplastic astrocytoma. Eight patients had received prior nitrosoureas. SWOG performance status was 1 in 11 patients and 2 in 22. The median age was 51 years (25-75 years). One patient had a partial remission (3%:95% confidence interval: 1%-16%). Twenty two patients had progressive disease. The median survival was 5.9 months. Toxicity was primarily gastrointestinal with nausea and vomiting in 13 patients and nausea only in 11 patients. Hepatotoxicity occurred in 10 patients. Echinomycin given at this dose and schedule is not effective in treating patients with recurrent or progressive glioblastoma multiforme or anaplastic astrocytomas.
Subject(s)
Brain Neoplasms/drug therapy , Echinomycin/therapeutic use , Glioma/drug therapy , Adult , Aged , Drug Administration Schedule , Echinomycin/adverse effects , Female , Glioma/mortality , Humans , Male , Middle Aged , Survival RateABSTRACT
Twenty-one patients with nonresectable refractory meningiomas were registered on a study giving tamoxifen 40 mg per M2 b.i.d. for four days, then 10 mg b.i.d. thereafter. Nineteen were eligible and evaluated for response. One patient (5%) achieved an MRI-documented partial response while two had a minor response measured on CT scan which was of short duration (4 and 20 months). Six patients (32%) remained stable for a median duration of 31 + months while ten (53%) demonstrated progression. Twenty-two percent (22%) reported subjective improvement though this did not correlate with objective improvement in all cases. At present, a definite recommendation for the use of tamoxifen in refractory meningiomas cannot be made. Further evaluation of hormonal therapy of meningiomas with a consensus for definition of endpoints for evaluation of response in view of the difficulty of evaluating radiologic findings with clinical outcome, is needed.
Subject(s)
Meningeal Neoplasms/drug therapy , Meningioma/drug therapy , Tamoxifen/therapeutic use , Female , Humans , Male , Meningeal Neoplasms/epidemiology , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/surgery , Meningioma/epidemiology , Meningioma/radiotherapy , Meningioma/surgery , Salvage Therapy , Tamoxifen/administration & dosage , Treatment OutcomeSubject(s)
Antineoplastic Combined Chemotherapy Protocols/toxicity , Dacarbazine/toxicity , Interleukin-2/toxicity , Melanoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dacarbazine/administration & dosage , Drug Evaluation , Female , Humans , Interleukin-2/administration & dosage , Male , Melanoma/pathology , Middle Aged , Neoplasm Staging , Outpatients , Sex CharacteristicsABSTRACT
Novobiocin, a commercially available oral antibiotic, inhibits DNA topoisomerase II in a manner shown in cell culture to enhance the cytotoxicity of alkylating agents and cisplatin. Thirty-six patients were entered on a Phase II trial using high-dose cisplatin (100 mg/m2 on days 1 and 8 for four cycles) after steady-state dosing with novobiocin (1000 mg or four 250-mg capsules every 12 hours for six doses, four of which were administered before each dose of cisplatin). One patient remains on study and cannot be evaluated for response. No complete responses were seen. Three patients (8%) had partial responses and an additional patient had an unconfirmed partial response. The median survival time of all patients was just less than 7 months. These results are comparable with those of other concurrent Southwest Oncology Group (SWOG) Phase II and III trials of high-dose cisplatin in non-small cell lung cancer (NSCLC). Novobiocin plasma levels were obtained for three patients and were approximately 50% of the optimal concentration as reported in cell culture for potentiation of cytotoxicity. It was concluded that an optimum test of novobiocin as a modulator of cytotoxicity may require the availability of an intravenous preparation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/administration & dosage , Lung Neoplasms/drug therapy , Novobiocin/administration & dosage , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capsules , Cisplatin/adverse effects , Drug Evaluation , Female , Humans , Infusions, Intravenous , Kidney/drug effects , Male , Middle Aged , Novobiocin/adverse effects , Novobiocin/blood , Remission Induction , Southwestern United StatesABSTRACT
The purpose of this Phase II pilot study was to determine whether a dose-intensive regimen of weekly cisplatin combined with other active non-cross-resistant agents would improve the response rate and survival time of patients with extensive non-small cell lung cancer. Patients received cisplatin (50 mg/m2/wk) on days 1, 8, 15, 22, 36, 43, 50, and 57 combined with mitomycin C (8 mg/m2) on days 1 and 36, vinblastine (3 mg/m2) on days 8 and 43, and 5-fluorouracil (5-FU) (1 g/m2) by continuous infusion over 24 hours on days 15 and 50. Responding patients received consolidation therapy with cisplatin and etoposide (VP-16). Of 82 registered patients, 80 were eligible and 77 were evaluable for response. The overall response rate was 23% with 1 patient achieving a complete response (CR) and 17 patients achieving a partial response (PR). The median survival time was 4.6 months. The toxicity profile was not different from that described for standard-dose regimens. Although this regimen does not offer any benefit over standard-dose cisplatin regimens for patients with extensive non-small lung cancer, the weekly schedule permits a dose-intensive regimen with acceptable toxicity for tumors that may benefit from this approach.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drug Administration Schedule , Drug Evaluation , Female , Fluorouracil/administration & dosage , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Mitomycin , Mitomycins/administration & dosage , Pilot Projects , Remission Induction , Survival Rate , Vinblastine/administration & dosageABSTRACT
105 patients with advanced ovarian cancer previously treated with cisplatin or carboplatin were entered into a study of iproplatin as second-line therapy. Patients were either clinically resistant to cisplatin or carboplatin, or had relapsed after complete response to these agents. Patients were treated intravenously at an initial dosage of 270 mg/m2 with dosage adjustments to 340, 200 or 135 based on observed toxicity. Of 101 eligible patients, 7 responses (3 complete, 4 partial; 12%) were observed in 60 patients resistant to cisplatin. 2 partial responses (11%) occurred in 18 patients resistant to carboplatin. 2 complete and 3 partial responses were observed in 19 patients (26%) previously treated with but not resistant to cisplatin. Response durations were 2-20 months. Toxicities of iproplatin included thrombocytopenia in 93% of patients, leukopenia in 76% of patients, anaemia in 68% of patients, and diarrhoea in 40% of patients. Thus iproplatin shares cross-resistance with cisplatin and carboplatin in the treatment of ovarian cancer and is not recommended as an effective second-line agent for platinum-resistant ovarian cancer.