Phase II study of pegylated liposomal doxorubicin and carboplatin in patients with platinum-sensitive and partially platinum-sensitive metastatic ovarian cancer.

OBJECTIVE: This phase II study assessed the activity and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin in relapsed ovarian cancer (ROC). METHOD: Forty women with platinum-sensitive and partially platinum-sensitive ROC were treated with PLD 50 mg/m2 plus carboplatin area under the curve 5 every 28 days in this South African multicenter study. All patients who completed 3 cycles of chemotherapy were evaluated for response. Primary outcome was response in the intent-to-treat population. RESULTS: Complete response was 35%, and partial response was 32.5% (overall response, 67.5%). Median time-to-progression was 11.9 months, and median survival was 30.0 months. Overall response was higher in platinum-sensitive (81%) versus partially platinum-sensitive patients (53%), as were median duration of response, median time-to-progression, and median survival. Treatment was well tolerated, with no grade 4 nonhematologic toxicities. Grade 3/4 hematologic toxicities included leukopenia (58%), neutropenia (55%), and thrombocytopenia (43%). CONCLUSION: Pegylated liposomal doxorubicin plus carboplatin is well tolerated and active in the treatment of platinum-sensitive and partially platinum-sensitive ROC.

Intranasal buserelin in the treatment of advanced prostatic cancer: a phase II trial.

Thirty-five patients with advanced prostatic cancer were entered in a trial of nasally administered gonadotropin-releasing hormone analogue agonist (GnRHA) buserelin. Four patients were unevaluable for response and toxicity. Twenty-five patients responded to treatment, two with complete remissions, 12 with partial remissions, and 11 who improved. The median baseline value for testosterone was 14.4 nmol/L. After 1 week of treatment, the median value was 10.8 nmol/L, while after 1 month the median value had decreased to 1.1 nmol/L (normal, 10.0 to 34.7). It is concluded that intranasal buserelin is an effective, simple, and safe method to achieve androgen deprivation in the treatment of advanced prostate cancer and is an alternative to orchiectomy and more acceptable than daily subcutaneous injections.

Breast cancer incidence in South Africa.

Cancer in South Africa is an emerging health problem, with breast cancer being one of the leading cancers in women, following similar worldwide statistics. Lifetime risks of developing breast cancer vary from a low of one in 81 in African women (similar to Japan) to a high of one in 13 among white women, similar to rates in Western countries. Age and stage at diagnosis vary considerably between the different races and populations (urban v rural) living in South Africa. Many different determinants (socioeconomic, cultural, geographic accessibility to medical centers with oncologic services, availability of traditional healers, and so on) affect patients with breast cancer (mainly rural black women) in their decisions to obtain early medical help as well as to refrain from the proposed therapeutic methods (surgery, radiotherapy, and chemotherapy). A brief overview of breast cancer in South Africa with special reference to some of the above determinants is presented.

Malignant pleural mesothelioma: a disease unaffected by current therapeutic maneuvers.

From 1965 to 1985, 262 patients with malignant pleural mesothelioma were treated with cytostatics only; radiotherapy (RT); RT and cytostatics; or decortication plus RT plus cytostatics. The median survival (MS) from diagnosis was 9.6 months. This was similar for all comparable treatment groups. In a univariate analysis, significant favorable prognostic factors were good performance status (PS), duration of symptoms greater than 6 months at the time of diagnosis, early stage of disease, white race, and female sex. In a multivariate analysis, PS, race, duration of symptoms, and stage were of significance for a favorable prognosis. Age, pain as first symptom, histologic subtype, and RT dose were not of prognosis significance in this study. The stepwise addition of treatment modalities did not increase survival, which remained the same as that reported for untreated patients. Therefore, phase II trials of new agents offer the only hope for advance in the treatment of this disease.

A randomised trial of vindesine plus interferon-alpha 2b compared with interferon-alpha 2b or vindesine alone in the treatment of advanced malignant melanoma.

60 patients were entered into a randomised study comparing vindesine (3 mg/m2/week) plus interferon-alpha 2b (6 U/m2 3 times per week) to vindesine alone or to interferon alone for the treatment of metastatic malignant melanoma. Patients receiving the combination therapy arm (schedule A; vindesine plus interferon-alpha 2b) showed a complete and partial response rate of 8/20 (40%) which was significantly higher (P < 0.05) than that achieved with either single-agent treatment schedule. In addition, patients receiving the combined treatment schedule had a significantly prolonged survival (median 19 months) when compared to a median of 10 months for interferon alone and 5 months for vindesine alone. The combination was generally well tolerated with only additive toxicity. It is concluded that combination treatment regimens utilising interferons together with chemotherapeutic agents deserve further study in the treatment of metastatic malignant melanoma.

Assessment of ventricular function by radionuclide angiography in patients receiving 4'-epidoxorubicin and mitoxantrone.

Serial assessment of ventricular function by means of radionuclide angiography was performed in 50 patients with malignant neoplasms who received either 4'-epidoxorubicin or mitoxantrone for longer than 3 months. In 9 of 30 patients given 4'-epidoxorubicin, a decrease of greater than or equal to 10% in the left ventricular ejection fraction (LVEF) was documented at doses of 143-1200 mg/m2. Two patients developed clinical signs of cardiotoxicity at a dose of greater than 1000 mg/m2. In 6 of 20 patients given mitoxantrone a decrease of greater than or equal to 10% in the LVEF occurred at doses of 26-98 mg/m2.

A phase II study of m-AMSA in patients with malignant mesothelioma.

Nineteen patients with histologically confirmed malignant mesothelioma were treated with m-AMSA at the University of Pretoria. All patients had evaluable disease and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-3. m-AMSA 120 mg/m2 was given IV every 3 weeks. Hematopoietic suppression was the major side-effect. Eleven patients developed leukopenia. There was one partial response (16 weeks), and a no change status was documented in 12 patients (median duration of 20 weeks). The median survival time of patients was 27 weeks from entry on study. Radionuclide ventricular ejection fraction tests were performed to evaluate cardiac function.

Phase II trial of i.v. vinorelbine and cisplatin in inoperable locally advanced or disseminated non-small-cell lung cancer: the South African experience.

PURPOSE: This multicentre phase II trial was conducted in South Africa to evaluate the activity of a combination of vinorelbine, administered in a new schedule, and cisplatin, in chemonaive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1995 and December 1996, 35 patients were enrolled. All patients had at least one bidimensionally measurable lesion. Vinorelbine was administered intravenously on day 1 and day 8 at a dose of 30 mg/m2 and cisplatin was administered intravenously on day 1 at a dose of 100 mg/m2. The chemotherapy cycle was repeated every three weeks. RESULTS: Of 35 evaluable patients, 14 (40%) achieved a response (one complete response and 13 partial responses). The median time to progression was 6.4 months (range 12-572 days) and the median survival was 15.7 months (range 12-882+ days). One-year survival was 56%. Toxicity was manageable and consisted of nausea and vomiting (grade 3 in 45% of patients) and grade 3-4 neutropenia seen in 13 patients with three patients experiencing grade 3 infection. Other side-effects were mild, including constipation grade 3 in 9.1%. A total of 153 courses were administered with patients receiving a median dose intensity of 81.7% for vinorelbine, while that of cisplatin was 74.1%. CONCLUSION: The combination of vinorelbine and cisplatin demonstrated substantial activity in terms of objective response and survival with manageable side-effects in patients with advanced NSCLC. These findings confirm the data from previous randomised studies. Further studies are ongoing in order to evaluate the efficacy of this combination in the neoadjuvant and adjuvant setting.

First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study.

The aim of this multicentric phase II study was to investigate the efficacy and toxicity of a combination of chemotherapy containing paclitaxel (Taxol) and a novel compound, a liposomal encapsulated doxorubicin (Caelyx), as first line therapy for patients with metastatic breast cancer. Thirty-four patients with advanced breast cancer were treated with a combination of paclitaxel 175 mg/m2 and liposomal doxorubicin 30 mg/m2, every 3 weeks. The combination chemotherapy was effective in 73% of the patients (ITT) (95% CI 55-86%) (7 complete and 18 partial responses). Grade 3/4 toxicities were documented in a small number of patients. Two toxic deaths (6%) were documented, one a hepatorenal failure and another a febrile neutropenia. One patient experienced pulmonary embolism but continued on treatment after appropriate therapy. The combination of paclitaxel and liposomal encapsulated doxorubicin induces a high and durable response rate with a moderate toxicity profile.

Oral idarubicin in combination with cytosine-arabinoside in previously untreated patients with acute non-lymphocytic leukemia.

Twenty-six previously untreated patients with acute non-lymphocytic leukemia (ANLL) were treated with oral idarubicin and cytosine-arabinoside (Ara-C). The median age of the patients was 44 years (range, 11-72). In 23 of the 26 patients a hypoplastic marrow, with a peripheral white cell count of less than 1,000/mm3 after treatment, was documented. Treatment was well tolerated with minimal symptoms of nausea and vomiting. Diarrhea was observed in three patients and stomatitis in nine patients. Alopecia was documented in only six patients. A complete remission (CR) was obtained in 12 patients (median duration 25 weeks). The median time to CR was 3.4 weeks (range, 1.4-5). Ten of the 26 patients were alive 6 months after the start of induction treatment, while a further four patients who were in the study for less than 6 months are alive and in remission at 5, 4, 3, and 3 months, respectively. Eight of 12 patients in whom bone marrow aplasia was documented achieved a CR; perhaps the drug dosages used in this study were suboptimal.

A randomized, placebo-controlled, double-blind phase 2 study of docetaxel compared to docetaxel plus zosuquidar (LY335979) in women with metastatic or locally recurrent breast cancer who have received one prior chemotherapy regimen.

PURPOSE: To determine if concomitant administration of docetaxel plus zosuquidar.3HC1 can prolong progression-free survival in patients with metastatic breast cancer. METHODS: A randomized, double-blind, multicenter, placebo-controlled clinical trial comparing docetaxel plus 500 mg zosuquidar.3HCl (DZ) with docetaxel plus placebo (DP). RESULTS: A total of 170 patients were enrolled and randomly assigned to treatment. The median age was 53 years (range, 31-74 years). 81.7% of patients had prior chemotherapy in the adjuvant setting and 18.3% in the neoadjuvant setting. The median progression-free survival time was statistically different between groups [7.2 months (DZ) vs. 8.3 months (DP)]. Once the stratification factor relative to progression following prior chemotherapy was considered, no significant treatment difference existed. CONCLUSION: The combination of zosuquidar.3HCl plus docetaxel is safe. The analysis of efficacy data is complex, but it can be concluded that there is no difference in progression-free survival, overall survival, or response rate in the study as a whole.

Cardiotoxicity of 5-fluoro-uracil. A case report.

A case of cardiotoxicity caused by 5-fluoro-uracil administration is described. The aetiological process is not clear, and it is possible that 5-fluoro-uracil has a vasoconstrictive effect on the coronary artery system.

Phase II study of 4'-deoxydoxorubicin in advanced colorectal cancer.

Thirty-three patients with advanced colorectal cancer were entered on a phase II study of 4'-deoxydoxorubicin (esorubicin) (30-35 mg/m2 q 3 weekly). Objective response was documented in 4 of 25 previously untreated patients and in none of 8 previously treated patients. Toxicity was acceptable with grade 3 or 4 leukopenia occurring in 8 patients. Complete alopecia occurred only in 4 patients and gastro-intestinal toxicity was mild. A significant decrease (greater than 10%) of the left ventricular ejection fraction occurred in 8/23 patients who received greater than 2 courses of treatment.

Nasally administered buserelin inducing complete remission of lung metastases in male breast cancer.

A 60-year-old man with bilateral lung metastases from breast cancer was treated with the gonadotropin-releasing hormone analogue, buserelin, given as an intranasal spray. Androgen deprivation and complete remission of lung metastases were achieved with minimal side effects. Androgen deprivation by means of nasally administered buserelin offers an easy and efficient alternate approach in the treatment of metastatic male breast cancer.

Radionuclide angiographic monitoring in patients treated with potentially cardiotoxic cytostatic drugs.

A prospective study of 120 patients with cancer was carried out to evaluate the effects of potentially cardiotoxic anticancer drugs using radionuclide cardiovascular studies. Five groups were studied: 7 patients received 4'-demethoxydaunorubicin, 23 4'-deoxydoxorubicin, 34 4'-epidoxorubicin, 49 mitoxantrone and 7 4'-(9-acridinylamino)-methan-sulphon-m-anisidide (amsa). Two patients receiving 4'-demethoxydaunorubicin, 7 on 4'-deoxydoxorubicin, 11 on 4'-epidoxorubicin, 21 on mitoxantrone and 3 on amsa had falls of greater than or equal to 10% in their left ventricular ejection fraction. Using data from this study, the recommended guidelines are set out.

Chronic granulocytic leukemia, neutrophilic type, with paraproteinemia (IgA type K).

A patient with chronic granulocytic leukemia, neutrophilic type, was followed for 28 months. A paraproteinemia, IgA type K, and Bence Jones proteinuria (K) appeared without prior chemotherapy with alkylating agents.

Amsacrine cardiotoxicity: assessment of ventricular function by radionuclide angiography.

Serial assessment of ventricular function by means of a nuclear medicine technique was performed in six patients with malignant disease receiving chemotherapy with amsacrine. Two patients who received treatment long enough so that greater than 580 mg/m2 of the drug was administered showed a significant decrease in left ventricular ejection fraction. Four patients who received total doses of 325-510 mg/m2 of amsacrine did not experience significant change in their cardiac function.