First-line chemotherapy with docetaxel and cisplatin in metastatic breast cancer.

The purpose of this study was to evaluate the efficacy and tolerance of combined treatment with docetaxel-cisplatin as first-line chemotherapy in patients with metastatic breast cancer (MBC). Consecutive eligible chemonaive patients received docetaxel 75 mg/m(2) on day 1 and cisplatin 75 mg/m(2) on day 2 every 3 weeks for 6 cycles, with prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) on days 4-11. Thirty-two patients (64%) had received prior adjuvant chemotherapy; these included 16 (32%) who had received anthracyclines. In 50 evaluable patients with a median age (range) of 56 (31-72) years, the overall response rate was 68% (95% CI, 55-81%), with 7 (14%) complete and 27 (54%) partial responses. Stable and progressive disease was observed in 10 (20%), and 6 (12%) patients, respectively. The median duration of response was 10 months, and the median time to progression was 39 weeks. Grade 3/4 hematological toxicity included--neutropenia in 9 patients (18%), anemia in 2 (4%) and thrombocytopenia in 1 (2%). One patient (2%) with febrile neutropenia required hospitalization. Grade 3/4 nonhematological toxicities included nausea/vomiting in 18%, nephrotoxicity in 14%, asthenia (4%), and neurotoxicity (2%). Toxicity was common in older patients (>56 years). There were no treatment-related deaths. A combination of docetaxel-cisplatin with rHuG-CSF support is well tolerated and effective as first-line chemotherapy in MBC.

Combined treatment with low-dose interferon plus vinblastine is associated with less toxicity than conventional interferon monotherapy in patients with metastatic renal cell carcinoma.

The outcome of treatment of advanced renal cell carcinoma is disappointing. In interferon (IFN)-treated patients, the high incidence of adverse effects causes many patients to withdraw from treatment. This 12-week randomized study compared the incidence of toxicity associated with high-dose IFN monotherapy (15 x 10(6) U thrice weekly) and treatment with the combination of low-dose IFN (5 x 10(6) U thrice weekly) and 6 mg/m2 vinblastine (VBL) every 14 days in 100 consecutive patients. There was no significant difference in response rate between treatment arms (42% IFN vs. 34% IFN + VBL) or between subgroups (by tumor location). Combined treatment was associated with a significantly lower incidence of fever, fatigue, and weight loss but with a higher incidence of leukopenia. There was no significant difference in the incidence of other events. More patients treated with IFN monotherapy required bed rest, and overall treatment costs were 60% higher than for combined treatment. It is concluded that combined treatment with low-dose IFN and VBL, without loss of short-term efficacy, is better tolerated and less expensive than high-dose IFN monotherapy.

Gemcitabine and vinorelbine as second-line therapy in non-small-cell lung cancer after prior treatment with taxane+platinum-based regimens.

Treatment options in patients with recurrent non-small-cell lung cancer (NSCLC) remain limited as a result of the poor activity of older agents after platinum-based therapy. The present phase II study aimed to evaluate the combination of gemcitabine and vinorelbine in patients with relapsed NSCLC after pretreatment with taxane+platinum-based regimens, since gemcitabine has demonstrated activity in that setting and the combination has been well tolerated in previous phase I/II studies. Patients with advanced NSCLC (stages III/IV), World Health Organization (WHO), Performance Status (PS) < or = 2, prior platinum+taxane-based chemotherapy and unimpaired haematopoietic and organ function were eligible. Chemotherapy was administered as follows: vinorelbine 25 mg/m(2) followed by gemcitabine 1000 mg/m(2), both administered on days 1 and 8, recycled every 3 weeks. 40 patients were entered and 39 were evaluable for response and all 40 for toxicity: median age was 61 years (range 50-72 years), median PS=1 (range 0-2), gender ratio=37 males/3 females, stages at initial diagnoses were IIIA=2, IIIB=14, IV=24. Metastatic sites included: lymph nodes: 23, bone: 4, liver: 5, brain: 4, lung nodules: 9, adrenals: 8, pleural effusion: 4. 22 patients had prior paclitaxel/ifosfamide/cisplatin treatment. Objective responses were; partial response (PR): 9/40 (22.5%), stable disease (SD): 13/40 (32.5%) and progressive disease (PD) 18/40 (45%). The median time-to-progression (TTP) was 4.5 months (range 1-17 months) and median survival 7 months (range 2-17+ months). 1-year survival was 17%. Grade 3 neutropenia was seen in 33% of patients. There was no grade 4 neutropenia and no episodes of febrile neutropenia. No grade 3/4 thrombocytopenia or grade 3/4 other non-haematological toxicities were observed. The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC failing prior taxane/platinum therapy. This regimen represents a tolerable and effective combination to apply in the palliative treatment of relapsed NSCLC.

Germ line BRCA1 & BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed.

BRCA1 and BRCA2 genes were screened for loss-of-function mutations in a series of 85 patients having at least one first- or second-degree relative affected by breast and/or ovarian cancer. All BRCA1 exons and BRCA2 exons 10 and 11 were screened with a combination of methods including SSCP, PTT and direct sequencing. We have found disease-associated mutations in 14 families (16.5%), eleven in BRCA1 and three in BRCA2. The known founder mutation 5382insC of BRCA1 was identified in seven unrelated families. The other mutations identified include the non-sense R1751X, the splice junction variant 5586G>A of BRCA1 and three frameshifts, 2024del5, 3034del4, and 6631del5, of BRCA2. Nine out of these 14 families had a family history of three or more breast/ovarian cancer cases. A large number of polymorphic or unclassified variants is also reported. Combined with our previously published data 5382insC was found in nine out of 20 families (45%), suggesting that this mutation may represent a common founder mutation in the Greek population.

Oral estramustine and oral etoposide for hormone-refractory prostate cancer.

OBJECTIVES: Estramustine and etoposide have been shown to inhibit the growth of prostate cancer cells in experimental models. An in vivo synergism of the two agents, when administered to patients with metastatic prostate cancer refractory to hormone therapy, has been reported. To confirm these results, we administered this combination to a large number of patients with hormone-refractory prostate cancer (HRPC). METHODS: Fifty-six patients with metastatic HRPC were treated with oral estramustine 140 mg three times a day and oral etoposide 50 mg/m2/day for 21 days. Therapy was discontinued for 7 days and the cycle was then repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. To control for the possible interference of an antiandrogen withdrawal effect, all patients discontinued antiandrogen therapy and were not enrolled in the study unless there was evidence of disease progression. RESULTS: Forty-five percent of 33 patients with measurable soft tissue disease demonstrated an objective response, which included five complete and ten partial responses. Among 52 patients with osseous disease 17% showed improvement and 50% showed stability of bone scan. Thirty patients (58%) demonstrated a decrease of more than 50% in pretreatment prostate-specific antigen (PSA) levels. The median survival of all patients was 13 months. Good pretreatment performance status, measurable disease response, improvement or stability of bone scan, and PSA response were important predictors of longer survival. CONCLUSIONS: We conclude that the combination of estramustine and etoposide is an active and well-tolerated oral regimen in HRPC.

Phase II study of temozolomide in patients with relapsing high grade glioma and poor performance status.

Temozolomide (SCHS2.365), an oral alkylating agent which penetrates the blood-brain barrier, evolved as an alternative to dacarbazine. The aim of this study was to evaluate the efficacy and safety of temozolomide in terms of overall survival, progression-free survival, clinical benefit and health related quality of life in symptomatic patients with relapsing malignant glioma and a poor performance status. Eleven patients were enrolled in the study. The median age was 44.6 years. Patients were treated with temozolomide per os at a dose of 150-200 mg/m2 daily for 5 consecutive days. Each cycle was repeated every 28 days. The median number of courses given per patient was 3.5. Nine patients were assessable for response. All patients were evaluable for toxicity. Based on radiographic findings 4 patients had stable disease (2 patients after a total of 16 cycles, and 2 patients after a total of 10 cycles). Four patients had progressive disease after 2 to 4 cycles. Of these 3 patients demonstrated a clinical benefit and one patient died after 3 cycles of treatment. Six patients had a significant clinical benefit even after 2 cycles of treatment with improvement of their neurological and performance status. Hematologic toxicity Gr II-III occurred in 3/9 patients. Nonhematologic toxicity consisted of Gr I nausea, and vomiting. In conclusion temozolomide appears to be a useful alternative for patients with relapsing malignant glioma after radiation and surgery and a poor performance status with little or no toxicity and considerable clinical benefit.

Chemotherapy of ovarian cancer.

Chemotherapy using a modified Cooper's regimen was applied during the past few years on 41 cases of advanced cancer of the ovary. We believe this scheme has not been attempted elsewhere. Twenty-five cases (60%) responded positively to this regimen. Two patients with generalized ovarian cancer may be cured. The combination of palliative surgery and polychemotherapy in cancer of the ovary may prove to be one of the most effective multidisciplinary approaches to generalized cancer.

Complete remission of a reccurrent mesenteric liposarcoma with rare histological features following the administration of trabectedin.

The present study describes a rare case of a mesenteric liposarcoma that resulted in a complete remission (CR) following treatment with trabectedin (Yondelis®). The patient presented with abdominal pain and fever. An abdominal mass was identified that corresponded to a mixed-type high-grade mesenteric liposarcoma with wide areas of necrosis, areas of dedifferentiation and features of a leiomyosarcoma. Three months after the removal of the first mass, the patient underwent a second laparotomy, followed by treatment with doxorubicin and ifosfamide. Subsequently, the patient was started on therapy with trabectedin and a CR was noted following only four cycles of therapy. The best responses that are reported in the literature for cases of liposarcoma treated with trabectedin are mostly for liposarcomas of the myxoid/round cell type and are mainly partial responses. In the present study, trabectedin was used for the treatment of a mesenteric liposarcoma of mixed morphological features and a CR was achieved.

Needle salpingoneostomy: an atraumatic surgical technique to correct a terminal obstruction of the tubes.

In 50 cases operated on restorative tubal surgery was performed applying an atraumatic technique with a fine needle to create a new opening of the ostium. Resection of the terminal part of the tube was avoided and an extraversion of the ostium fibria was accomplished by careful manipulation. Neither electrocautery nor hydrotubation was used during the operation. Our results were the following: 1. Thirteen (13) cases with intrauterine pregnancy. Twenty-nine (29) cases with viable tubal patency. Four (4) cases which a new obstruction. Four (4) cases which have not returned for re-examination 1.