Antonio Gabriele

Cisplatin-, epirubicin- and paclitaxel-containing chemotherapy in uterine adenocarcinoma

PURPOSE To evaluate the toxic effects and antitumour activity of a multidrug regimen with cisplatin, epirubicin and paclitaxel (CEP) as initial therapy in patients with uterine adenocarcinoma. PATIENTS AND METHODS Forty-nine patients with histologically-confirmed diagnoses of locally advanced, recurrent or metastatic cervical or endometrial adenocarcinoma entered the study. Treatment consisted of epirubicin (E) given at 70 mg/m2 followed by paclitaxel (P) (175 mg/m2 over three hours) and cisplatin (C) (50 mg/m2), repeated every three weeks. Eligibility criteria also included age < or = 75 years, no previous chemotherapy, no previous radiotherapy to the tumour parameters, bidimensionally-measurable lesions, no previous or ongoing cardiac disease, and renal and liver function within normal limits. Complete blood cell counts were repeated weekly, and tumor response was assessed every three cycles. A maximum of eight courses was administered in responding patients. RESULTS From January 1996 to January 1997, 30 patients with endometrial adenocarcinoma and 19 with cervical adenocarcinoma entered the study, for a total of 213 cycles of treatment. In patients with endometrial carcinoma the overall clinical and pathological response rates were 73% (95% CI, range 54%-88%) and 35% (95% CI, range 16%-57%) respectively; in patients with locally advanced cervical carcinoma the overall clinical and pathological response rates were 64% and 62%. WHO grade 3-4 neutropenia occurred in 61% of the patients, with one possible toxic death. Retreatment had to be delayed for at least one week because of persisting neutropenia in 34% of the patients. Mild peripheral neuropathy and stomatitis were observed in 46% and 23% of the patients. One patient presented acute congestive heart failure after the third cycle of treatment. CONCLUSION The high antitumour activity and the good tolerability of CEP suggest that this regimen should be prospectively compared to standard combinations as initial treatment of advanced endometrial carcinoma.

Paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy for recurrent or persistent squamous-cell cervical cancer

PURPOSE The results of salvage chemotherapy for recurrent or persistent squamous-cell cervical cancer are unsatisfactory. Cisplatin and Ifosfamide are effective compounds in cervical cancer. Paclitaxel has recently been tested with promising results. The aim of this study was to assess the efficacy of a combination of paclitaxel, ifosfamide and cisplatin (TIP) for persistent/recurrent squamous-cell cervical carcinoma in a phase II trial. PATIENTS AND METHODS Forty-five women were treated with the TIP regimen. Thirty-one had received prior irradiation. Paclitaxel was given at a dose of 175 mg/m2, ifosfamide at a dose of 5 g/m2, and cisplatin at a dose of 75 mg/m2 (50 mg/m2 in irradiated patients) at three-week intervals. RESULTS We observed 15 clinical complete responses, 15 partial responses, 9 stable diseases and 6 progressions. The objective response rate was 67% (95% confidence interval: 51%-81%). Ten complete responders underwent subsequent surgery and seven had pathology-defined complete responses (two in irradiated areas). The response rate was 52% in irradiated and 75% in non-irradiated areas. The median survival for non-responders is 6 months, 9+ month for partial responders and 13+ for complete responders. The most relevant side effect was myelotoxicity, with 91% of patients experiencing grade 3-4. One woman had life-threatening toxic effects. CONCLUSIONS This combination is highly effective for salvage treatment in non-irradiated patients. For irradiated women the response rate is higher than that observed with other regimens but further investigation is warranted. The toxicity is relevant but adequate hydration and prolonged infusion of ifosfamide make it acceptable.

Complete remission of brain metastases from ovarian carcinoma with carboplatin

Central nervous system involvement by epithelial ovarian carcinoma is rare. We report the case of a 49 year old woman with stage IV serous carcinoma of the ovary who developed multiple cerebral and cerebellar metastases 7 months after achieving complete response to platin-based chemotherapy. Eight courses of carboplatin (400 mg/m2) were administered and after the second cycle complete remission of the brain deposits occured. The treatment afforded rapid subjective and objective relief and was associated with a good quality of life. Abdominal recurrent disease was diagnosed 22 months after treatment for brain involvement. Paltin-based chemotherapy was reinstated, but the patient died from progressive adbominal disease without any sign of cerebral involvement and any neurological symptomatology. Carboplatin should be considered for the treatment of ovarian carcinoma metastatic to the brain.

Treatment of fallopian tube carcinoma with cyclophosphamide, adriamycin, and cisplatin.

Primary carcinoma of the fallopian tube is uncommon; optimal primary treatment is still not well defined, and little information is available about the efficacy of cisplatin-based combination chemotherapy. Thirty-eight patients with fallopian tube carcinoma were treated with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and cisplatin (50 mg/m2) (CAP). Thirty-two patients received the combination chemotherapy as first-line treatment after cytoreductive surgery, whereas six subjects were treated for recurrent disease. The patients received a median of six cycles of therapy (range, four to nine). At the initiation of chemotherapy, 24 patients had measurable lesions. In this group of patients, 15 had a clinical complete response (CR), four had a partial response (PR), three had stable disease (SD), and two had progressive disease (PD) after chemotherapy. The overall clinical response rate (CR + PR) was 80%. Ten of the 14 CR patients who were submitted to second-look operation (SLO) were found free of disease, in pathologic complete response (pCR). Three pCR patients relapsed, and two of them died despite second-line treatment. Nine patients achieving PR, SD, and PD after first-line chemotherapy were further treated (five with chemotherapy, two with radiotherapy, two with progesteron), but none responded to second-line treatment and all died (median survival, 9 months). Fourteen patients without gross residual disease after cytoreductive surgery had no measurable lesions and were not evaluable for response. Seven of them had negative SLO and remain disease free. Three patients (two stage III and one stage II) who refused SLO relapsed 14, 16, and 26 months after completion of chemotherapy. The median survival for the entire group was 38 months, and the 5-year survival rate was 35%. The toxicity of the regimen was moderate. The CAP regimen appears to be active in primary fallopian tube carcinoma and yields response rates comparable to those reported for epithelial ovarian cancer.

HIV infection and invasive cervical carcinoma in an Italian population : the need for closer screening programmes in seropositive patients

ObjectiveTo evaluate in an Italian population the prevalence, characteristics at first diagnosis, and outcome of HIV-seropositive individuals with cervical carcinoma referred to a tertiary-care institution. DesignA retrospective evaluation of all patients referred for invasive cervical carcinoma from 1991 to 1994. SettingThe departments of obstetrics, and gynaecology, and radiotherapy at San Gerardo Hospital, University of Milan, Italy. PatientsA total of 340 women were treated over a 3-year period (186 aged < 50 years). Six patients were found to be HIV-seropositive. InterventionsSeropositive patients were treated according to current institutional protocols, irrespective of HIV status. Four underwent radiotherapy, and two radical hysterectomy as primary treatment. ResultsAlthough five HIV-seropositive patients were known to be infected 13–81 months before diagnosis of cervical cancer, none had received a PAP smear in the last year, and only one in the last 2 years. HIV patients were younger than general population (P= 0.02), with a significant history of intravenous drug use (P= 0.000001), and with more advanced disease (P=0.04). Two HIV-positive patients also received polychemotherapy (one adjuvant, and one salvage treatment), and both completed the planned treatment. Within 24 months two patients had died of cancer, and one of AIDS; one is alive with AIDS, and cancer, and two are free of disease. ConclusionsThis study confirms that in a southern European population, HIV- seropositive women present to tertiary-care institutions with more advanced disease, and have a poorer prognosis than the general population. Strict screening programs for cervical dysplasia, and cancer are warranted for HIV-seropositive patients.

Brain Metastases from a Primary Carcinoma of the Fallopian Tube

Central nervous system involvement by gynecological tumors is considered an uncommon event. Among 47 patients registered for tubal carcinoma in our institution between 1982 and 1994, 3 (6.4%) developed brain metastases. The median age at the time of the diagnosis of central nervous system metastases was 61 years. The median interval between diagnosis of tubal cancer and documentation of brain involvement was 37 months. All deposits were diagnosed as contrast-enhancing, space-occupying lesions on computed tomography scans. Two patients had cerebral metastases, 1 had cerebellar involvement. The central nervous system was the only site of recurrent disease in 1 patient 37 months after diagnosis of tubal carcinoma. The median survival from diagnosis of brain metastases was 1 month. Attention should be paid to the possibility of distant metastases associated with tubal carcinoma in order to treat these patients promptly.

Brachytherapy for isolated vaginal recurrences from endometrial carcinoma.

Aims and background Isolated vaginal recurrences of endometrial carcinoma are rare, and prognostic factors that predict treatment outcome are still not well defined. The aim of the present study was to evaluate the results of brachytherapy in isolated vaginal recurrences from endometrial carcinoma. Methods Thirty-five patients with isolated vaginal recurrences were treated with brachytherapy with intravaginal ovoids or cylinders that were calculated to deliver 6000 to 7000 cGy at the surface. Patients were assessed for size and location of recurrence at presentation, response and complications from therapy. Results Treatment was well tolerated by most patients. Grade 2 toxicity occurred in 4 patients (3 cases of partial vaginal stenosis and one proctitis). Complete response to radiation was observed in all patients, and an overall 9 failures were observed (4 local, 4 distant and 1 local plus distant). Twenty patients (57%) were alive without evidence of disease at 3 to 11 years following treatment. Site of vaginal recurrence (upper third versus others) and long (more than 12 months versus less than 12 months) interval from hysterectomy were the only factors significantly related to local failures. Conclusions Isolated vaginal recurrences following hysterectomy for endometrial carcinoma can be treated with brachytherapy with a low rate of severe toxicity.