Combination of High-Dose Chemotherapy, Autologous Bone Marrow/Peripheral Blood Stem Cell Transplantation, and Thoracoscopic Surgery in Refractory Nongestational Choriocarcinoma of a 45XO/46XY Female: A Case Report

A 39-year-old woman having a pure gonadal choriocarcinoma with lung metastasis was referred to our hospital after hysterectomy and bilateral salpingo-oophorectomy. She was found to have a 45XO/46XY karyotype and gonadal dysgenesis. The patient's serum β-hCG was normalized after six courses of chemotherapy with cisplatin and etoposide of conventional dose (100 mg/m², 100 mg/m²× 3 days), but began to fluctuate. Thoracoscopic resection of a remaining pleural lesion was negative for malignancy. However, the disease relapsed as multiple metastatic nodules in bilateral lung fields and the mediastinum. After one course of priming chemotherapy with conventional dose (1 g/m²cyclophosphamide, 400 mg/m²carboplatin, and 500 mg/m²etoposide), high-dose chemotherapy with a total dose of 1500 mg/m²carboplatin, 1200 mg/m²etoposide, and 5 g/m²ifosfamide followed by autologous bone marrow transplantation and peripheral stem cell support was given. Thoracoscopic surgery was performed to resect two residual solitary metastatic lung lesions. With these salvage treatments, the patient obtained complete remission and remained disease free at last follow-up (17 months). Our result suggests that high-dose chemotherapy may be effective in chemosensitive nongestational choriocarcinoma when first chemotherapy has failed.     

Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m²), doxorubicin (50 mg/m²), and cyclophos-phamide (500 mg/m²) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1–13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.     

Prophylactic Granulocyte Colony-Stimulating Factor Allows Escalation of Chemotherapeutic Dose Intensity in Advanced Epithelial Ovarian Cancer

Background: In an effort to discover an effective regimen for use in Phase III evaluation of the efficacy of dose intensification in advanced ovarian cancer, we performed a Phase II trial of dose intensified cisplatin, etoposide, and ifosfamide with granulocyte colony-stimulating factor (G-CSF). Methods: Thirty patients with primary, FIGO Stage 3 or 4, epithelial ovarian cancer underwent intensified cytoreduction followed by cisplatin 105 mg/m², etoposide 300 mg/m²and ifosfamide/mesna 3 g/m², q 28 days × 6 cycles with G-CSF 5 μg/kg q day for 7 days. The dose of etoposide and ifosfamide was escalated 20% in cohorts of three patients. Results: Intensified cytoreductive surgery was successful in resecting all gross tumor in 24 patients (80%). At the original dose of cisplatin, etoposide, and ifosfamide without G-CSF, 55% of cycles resulted in neutropenia and 38% in thrombocytopenia (dose INTENSITY = 0.8). With the addition of G-CSF, neutropenia developed in 5% of cycles and thrombocytopenia in 38%. At a 20% escalation of etoposide and ifosfamide, neutropenia developed in 17% of cycles and thrombocytopenia in 50% (dose INTENSITY = 1.2). At a 40% escalation of etoposide and ifosfamide, neutropenia developed in 33% of cycles and thrombocytopenia in 83%, which was dose limiting. The remaining 18 patients were treated at a 20% escalation and neutropenia developed in 14% of cycles and thrombocytopenia in 36%. CA125 response was 73%. At a 4.1-year median follow-up, median progression-free survival was 2.6 years and median survival was 3.0 years. Conclusion: In 30 women with primary advanced ovarian cancer, G-CSF allowed a 50% dose escalation of etoposide and ifosfamide from 0.8 to 1.2 dose intensity. The maximum tolerated dose of this regimen is cisplatin 105 mg/m², etoposide 360 mg/m², and ifosfamide 3.6 g/m²with G-CSF.     

Cisplatin,doxorubicin hydrochloride,and cyclophosphamide followed by radiotherapy in high-risk endometrial carcinoma

OBJECTIVE: Our purpose was to assess the effect of adjuvant platinum-based, multiagent chemotherapy followed by conventional radiotherapy on the recurrence-free interval, patterns of recurrence, and survival of women with completely resected, poor-prognosis endometrial carcinoma. STUDY DESIGN: Surgical stage IC and II endometrial carcinomas involving the outer one third of myometrium and completely resected stage III and IV carcinomas were eligible for six cycles of cisplatin (Platinol), doxorubicin hydrochloride (Adriamycin), and cyclophosphamide (Cytoxan) (50, 50, 500 mg/m²), followed by external beam radiotherapy to pelvis, pelvis and periaortic chain, or whole abdomen, on the basis of documented disease. RESULTS: Forty-seven women were registered between April 1, 1984, and Oct. 10, 1992; 39 were eligible for review. Six were stage I, 28 were stage III, and five were stage IV. Two tumors were grade I, eight were grade 2, and 29 were grade 3. Twenty-three were endometrioid adenocarcinomas, eight papillary serous, six adenosquamous, and two clear cell. Thirty-seven patients (94.9%) completed six courses of chemotherapy, with no deaths ascribed to treatment. Grade 3 or 4 neutropenia was experienced by 17 (44%) and sepsis by three (8%). Current median follow-up is 27.3 months. Fifteen patients (38.5%) have recurrence, and 14 have died after a median interval of 26.9 months. The 2-year progression-free interval is 72.5% for nonpapillary serous histologic types and 22.5% for papillary serous cancers (p = 0.0074). CONCLUSION: Adjuvant chemotherapy with Platinol, Adriamycin, and Cytoxan followed by radiation therapy is well tolerated and seems to confer a survival advantage to women with nonpapillary serous endometrial carcinoma with a poor prognosis compared with historic controls treated by surgery or radiotherapy. (AM J Obstet Gynecol 1994;170:1677-82.)     

Outcome and reproductive function after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP) for patients with ovarian endodermal sinus tumor

ObjectiveThe aim of this study was to investigate the outcome and reproductive function of patients with ovarian endodermal sinus tumor (EST) after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP).MethodsBetween 1995 and 2006, 1034 patients with the diagnosis of ovarian cancer were treated at a single institution. Among these patients, 51 had a confirmed diagnosis of malignant ovarian germ cell tumor (MOGCT) including 20 cases of EST. We retrospectively reviewed those patients with EST, who received BEP as adjuvant chemotherapy. The doses were 15 mg/day of bleomycin on days 1 to 3, 100 mg/m²/day IV of etoposide on days 1 to 3 and 20 mg/m²/day of cisplatin on days 1 to 5. The median number of total cycles was six (range between three and nine).ResultsThe median age of the patients with EST was 18 years (range 5 to 36). All except two were nulliparous. The overall survival rate was 90% at a median follow-up of 70 months. Two patients (10%) had disease recurrence in the pelvis. Of the 15 patients who were treated with fertility-sparing surgery, all had regular menstruation following the completion of adjuvant chemotherapy, and two of these patients had pregnancies with live birth deliveries and no complications.ConclusionIn patients with EST, the cumulative high-dose BEP regimen resulted in excellent overall survival and did not seem to impair ovarian function.     

Cisplatin/Etoposide Chemotherapy for Recurrent or Primarily Advanced Cervical Carcinoma

Thirty-eight women with primarily advanced (n= 10) or recurrent (n= 28) cervical carcinoma were treated with cisplatin (30 mg/m²/day intravenously) and etoposide (60 mg/m²/day intravenously) for 3 days followed by oral etoposide, 50 mg daily for 7 days, repeated at 28-day intervals. The response rate was 39% (95% confidence limits 24–55%) with response duration of 5 to 36 months. The main toxicities were neutropenia (21% developing neutropenic fever), alopecia, stomatitis, and nausea and vomiting. Despite this all responders had maintained or improved quality of life as defined by symptoms and performance status.     

Uterine Papillary Serous Carcinoma Treated with Intraperitoneal Cisplatin and Intravenous Doxorubicin and Cyclophosphamide

This study was designed to evaluate the efficacy of intraperitoneal cisplatin and intravenous doxorubicin and cyclophosphamide in patients with uterine papillary serous carcinoma. Sixteen patients with uterine papillary serous carcinoma underwent complete surgical staging and placement of an intraperitoneal port. Postoperatively, they received cisplatin (100 mg/m²) given intraperitoneally and doxorubicin (50 mg/m²) intravenously and cyclophosphamide (600 mg/m²) intravenously every 4 weeks for 6 cycles. The intraperitoneal ports did not function in 3 patients immediately following surgery. The remaining 13 patients constitute the study group. The patients ranged in age from 37 to 77 years. There were 1 patient with Stage IA, 3 with Stage IB, 2 with Stage IIB, 2 with Stage IIIA, 2 with Stage IIIC, 1 with Stage IVA, and 2 with Stage IVB. At the end of surgery no gross residual disease remained except for 1 patient who had less than 1-cm nodules in the peritoneal cavity. Eleven of the patients underwent 6 cycles of chemotherapy, 1 patient underwent 3 cycles, and 1 patient underwent 1 cycle. A total of 71 cycles of chemotherapy were given. All patients developed alopecia. Two patients developed neutropenic fever; one was treated with antibiotics, the other patient died from urosepsis. One patient had a >15% decrease in left ventricular ejection fraction which led to a dose reduction of doxorubicin. One patient had a urinary tract infection and one patient developed a port infection which necessitated its removal. Seven patients have died, 1 is alive with disease, and 5 patients are alive with no evidence of disease. Five of the 7 patients with extrauterine disease have died of disease. One is alive with disease and the other is free of disease. The median survival of these patients was 34 months with an overall 3 years survival of only 24.1%. Although the protocol was reasonably well tolerated, the overall survival did not differ from that of a similar group of patients treated at our institution with intravenous chemotherapy. There was a high incidence of dysfunction of the intraperitoneal ports (25%). This approach with intraperitoneal cisplatin presents no therapeutic advantage for these patients.     

High-Dose Platinum versus Standard Dose in Advanced Ovarian Carcinoma: A Randomized Trial from the Gynecologic Cooperative Group of the French Comprehensive Cancer Centers (FNCLCC)

Objective. The aim of this study was to evaluate the impact of platinum dose intensity on pathological response rate and overall survival in patients with advanced ovarian adenocarcinoma.Methods. Between February 1992 and December 1996, 195 previously untreated patients with FIGO stage IIb-c, IIIb-c, or IV with macroscopic residual disease after suboptimal debulking surgery were randomized to receive CCC (100 mg/m² of cisplatin, 300 mg/m² of cyclophosphamide, 300 mg/m² of carboplatin, n = 96) or CC (100 mg/m² of cisplatin, 600 mg/m² of cyclophosphamide, n = 99) for six courses at 28-day intervals. A second-look laparotomy was planned at the end of chemotherapy.Results. In the CCC arm, the platinum compound received dose intensity and relative total dose were 85 and 76%; in the CC arm, they were 94 and 85%. Grade 3–4 toxicity was more frequent in the CCC arm than in the CC arm for leukopenia (56% vs 26%, P < 0.001), febrile neutropenia (18% vs 4%, P = 0.002), anemia (31% vs 5%, P < 0.001), thrombopenia (55% vs 4%, P < 0.001), and ototoxicity (8% vs 0%, P < 0.001). The pathologic complete response rate was 22 and 14% in the CCC and CC arms, respectively (P = 0.19). With a median follow-up of 53 months, the median time to failure and the 3-year treatment failure-free survival rate were 17.4 months and 22% vs 13 months and 11% in the two arms, respectively (P = 0.01). The median survival time and the 3-year overall survival rate were, respectively, 30 months and 42% vs 25 months and 33% (P < 0.20).Conclusion. The platinum dose intensification (1.6-fold increase) obtained with the CCC association improves the treatment failure-free survival without significant impact on overall survival when compared with the CC regimen in suboptimal debulked ovarian adenocarcinoma. However, because of its high rate of hematologic toxicity and ototoxicity, this association cannot be recommended for routine practice.     

Clinical effects of irinotecan hydrochloride in combination with cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer

Objective

To evaluate the toxicity and efficacy of irinotecan plus cisplatin neoadjuvant chemotherapy (NACT) for cervical cancer.

Methods

A total of 120 cases with cervical cancer were divided into 2 groups and retrospectively reviewed: Sixty FIGO IB2-IIB patients in NACT group were treated with 2 cycles of irinotecan 60 mg/m² on days 1 and 8 plus cisplatin 60 mg/m² on day 1 followed by surgery. Sixty FIGO IB2-IIB patients in control group were treated directly with surgery.

Results

The 60 patients in NACT group received a total of 120 cycles. Grades III and IV neutropenia and diarrhea were seen in 15.8% and 11.7%, respectively, of all chemotherapy cycles. Six (10.0%) patients achieved complete remission, 33 (55.0%) achieved partial remission, 21 (35.0%) remained stable, and none had disease progression. Postoperatively the deep cervical stromal invasion and positivity of surgical margins were significantly fewer in the NACT group. The pelvic lymph node metastasis rate of responders to NACT was significantly lower than that of non-responders (12.8% vs 38.1%). With a median follow-up of 29 and 30 months, the intra-pelvic recurrence rate of the NACT group was significantly lower than that of the control group (3/60 vs 11/60, p = 0.023), the 2-year recurrence-free survival and the 2-year overall survival was 82.3% and 86.1% in the NACT group, and 86.3%, 87.9% in the control group with no significant difference. Multivariate analysis showed that response to NACT was the only factor associated with survival (p = 0.036).

Conclusion

Irinotecan plus cisplatin NACT for cervical cancer has high efficacy and tolerable toxicity, and can significantly reduce the rates of deep cervical stromal invasion and positive surgical margins. Pelvic lymph node metastasis decreases significantly in responders compared with non-responders. The response to NACT can be considered as an independent prognostic factor.     

High-risk metastatic gestational trophoblastic disease. A new dose-intensive, multiagent chemotherapeutic regimen.

Dose-intensive, multiagent chemotherapy for the treatment of high-risk gestational trophoblastic disease has evolved as the treatment of choice for these patients. High-dose methotrexate in combination with etoposide, dactinomycin, vincristine and cyclophosphamide (EMA-CO) has now been demonstrated to be superior to the traditional methotrexate, dactinomycin, cyclophosphamide chemotherapy in patients with prognostic scores of greater than or equal to 8. An attempt was made to improve upon the EMA-CO regimen by increasing the dose intensity of etoposide and adding cisplatin to the high-dose methotrexate, etoposide and dactinomycin. That regimen was used on four patients with ultra-high-risk gestational trophoblastic disease.     

Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma

Objective

Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin “sandwiched” with RT in patients with surgically staged and completely resected uterine carcinosarcoma.

Methods

Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m²/day × 5 days) with cisplatin (20 mg/m²/day × 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m²/day × 5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods.

Results

In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both ‘sandwiched’ with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p = 0.16), so they were combined for analysis. 19 patients (70%) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 ± 1.12 months; log-rank p = 0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 ± 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18%, 4% and 4% of cycles, respectively.

Conclusions

Ifosfamide “sandwiched” with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this ‘sandwich’ regimen comes with a moderate but tolerable toxicity profile.     

Etoposide-Platin Combination Therapy for Chemorefractory Gestational Trophoblastic Disease

The purpose of this study was to determine activity of etoposide-platin combination chemotherapy for chemorefractory gestational trophoblastic disease. A retrospective review of patients treated with etoposide-platin chemotherapy for chemorefractory trophoblastic disease was conducted. Patients received etoposide 100 mg/m² and cisplatin 20 mg/m² on Days 1 through 5 of 14- to 21-day cycles. Patient characteristics, responses, and toxicity were recorded. Seven women received etoposide-platin for chemorefractory disease. The median WHO prognostic index score upon initiation of therapy was 16 (range, 10-20) and patients had received a median 6 cycles of prior combination chemotherapy. Five patients developed grade IV neutropenia, four developed neutropenic sepsis, and two required platelet transfusions. Two patients developed significant deterioration of renal function. Six (86%) patients had complete responses, with normalization of hCG values, but only three (43%) patients with low pretherapy hCG levels have had sustained remissions. Etoposide-platin chemotherapy is an active regimen for the treatment of women with chemorefractory gestational trophoblastic disease but has significant hematologic and renal toxicity when used as salvage therapy. Future studies should investigate the incorporation of etoposide-platin into initial therapy of women with high-risk disease.     

The effect of prolonged cisplatin-based chemotherapy on progression-free survival in patients with optimal epithelial ovarian cancer: "maintenance" therapy reconsidered.

From 1978 until 1988, 116 patients with epithelial ovarian cancer were entered onto one of three consecutive prospective clinical trials involving cisplatin-based combination chemotherapy. They had the following characteristics: (1) stage III or IV disease, (2) grade 2 or 3 tumors, and (3) optimally debulked tumors (residual disease < or = 2 cm). The purpose of the study was to investigate the influence of duration of chemotherapy on survival. The treatment plans were as follows: Trial 1, 12 cycles of cisplatin/melphalan (43 patients); Trial 2, 12 cycles of cisplatin/cyclophosphamide (24 patients); and Trial 3, 6 cycles of cisplatin/cyclophosphamide (49 patients). The total dose of cisplatin was 60 mg/m2 in the first trial and 50 mg/m2 in the second and third trials. Median survival times for the three groups were 58, 29, and 35 months, respectively (NS). Median progression-free survival (PFS) times were 37, 23, and 15 months, respectively (P = 0.0008). Combining patients from the first two trials, the median PFS for patients receiving 12 planned cycles of chemotherapy was 30 months versus 15 months for patients receiving 6 planned cycles (P = 0.0004). Using a forward stepwise Cox proportional hazard model, the use of 12 cycles of therapy and melphalan predicted increased PFS (P = 0.0001 and P = 0.0002, respectively). In view of these results, the lack of published data supporting the superiority of 6 over 12 cycles of chemotherapy, and the rather recent availability of less toxic maintenance therapy (i.e., carboplatin), we believe that a multiinstitutional trial comparing the 6-cycle regimen with more prolonged chemotherapy is justifiable.     

Cycles of Dose-Intensive Chemotherapy with Peripheral Stem Cell Support in Persistent or Recurrent Platinum-Sensitive Ovarian Cancer

Objective.The objective was to determine the toxicity and surgically documented response rate of sequential high-dose chemotherapy with peripheral stem cell support in patients with persistent or recurrent cisplatin-sensitive ovarian cancer.Methods.Fourteen patients (average age, 45 years) were treated with cyclophosphamide (4.5 g/m²), followed by granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral stem cell harvests. The subsequent regimen prescribed three courses of carboplatin (1 g/m²) and cyclophosphamide (1.5 g/m²with 2-mercaptoethanesulfonate) every 2 weeks with stem cell support. This was followed by three courses of paclitaxel at 250 mg/m²every 2 weeks with G-CSF support only. Six patients were entered on the basis of a positive second-look laparotomy and 8 patients had a first recurrence after at least a 6-month disease-free interval.Results.Fourteen patients were entered and 12 patients completed all planned courses of therapy (mean time, 13 weeks). Normal hematopoiesis was reestablished after each cycle. Hospitalization for neutropenic fever occurred in 11/93 cycles (11.8%). Thirteen patients required blood transfusions and in 12 patients platelet transfusions were given. One patient had grade 3 neurotoxicity. An initial elevated CA 125 returned to normal in 7/8 patients (88%) and 71% of patients with measurable disease responded to therapy. There were 2 pathologic complete responders (PCR), making the PCR rate 2/14 or 14% (0–35%).Conclusion.Although this regimen was well tolerated and clinical response rates were high, the surgically documented response rate was not clearly superior to conventional salvage regimens in platinum-sensitive patients.     

Low-dose versus high-dose oxytocin augmentation of labor — A randomized trial

OBJECTIVE: Our purpose was to compare the efficacy and safety of low-dose versus high-dose oxytocin regimens in the augmentation of labor.STUDY DESIGN: Three hundred ten term pregnancies requiring augmentation of labor underwent randomization to receive either a low-dose or high-dose oxytocin augmentation regimen. Maternal demographics, labor-delivery data, and neonatal outcome were compared.RESULTS: The hgih-dose oxytocin group had a significant lower cesarean section rate, regarless of parity (10.4% vs 25.7%. p < 0.001), with no differences in maternal complications and neonatal outcomes. The time needed to correct the labor abnormality as also significantly decreased (1.24 ± 1.4 hours vs 3.12 ± 1.6 hours, p < 0.001) in the high-dose group.CONCLUSIONS: The use of a high-dose oxytocin regimen benefits both nulliparous and multiparous women requiring labor augmentation by significantly lowering both the time necessary to correct the labor normality and the need for cesarean section.     

A Phase I Study of Paclitaxel and Cyclophosphamide in Recurrent Adenocarcinoma of the Ovary

We have conducted a disease specific phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary. This was done to take advantage of the cellular and molecular synergism between paclitaxel and DNA-damaging agents, with the hope of avoiding paclitaxel–cisplatin toxicities. Paclitaxel was given as a 24-hr CIVI, after which cyclophosphamide was given as a 60-min infusion. Cycles of therapy were repeated every 3 weeks; and granulocyte colony-simulating factor (G-CSF) was given in a “flexible” dosing fashion. Starting doses were 170 mg/m²paclitaxel and 750 mg/m²cyclophosphamide. Dose-limiting toxicity (DLT) was seen at the doses of 250 mg/m²paclitaxel and 1250 mg/m²cyclophosphamide. DLT was cumulative thrombocytopenia. There were six nonhematologic grade 3 or 4 toxicities experienced in the study. Eleven of 20 evaluable patients (55%) have achieved an objective response (4 CCR;7 PR). Three of four CCRs were confirmed by negative findings at peritoneoscopy. The median number of prior therapies was 2 (range 1–4) and 17 individuals had platinum-refractory disease. We conclude that paclitaxel followed by cyclophosphamide is an active combination in recurrent ovarian cancer and that further study is needed to determine if this combination is truly better than paclitaxel alone.     

Standard dose cisplatin with rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer

We have investigated the feasibility of a program of autologous peripheral blood stem cell (PBSC) harvesting and transplantation in patients with ovarian cancer. From four patients, PBSC was collected during hematopoietic recovery following aplasia induced by standard dose cisplatin 70 mg m⁻² with etoposide 500 mg m⁻² or adriamycin 40 mg m⁻² and cyclophosphamide 500 mg m⁻² plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) at a dose of 75 µg day⁻¹ given intracutaneously. In apheresed patients, we harvested an average of 2.31 × 10⁵ kg⁻¹ colony-forming unit granulocyte/macrophage (range 0–5.22) per cycle. Low hematologic toxicity was observed during the hematopoietic reconstitution of the four patients subjected to PBSC support with G-CSF (5 µg kg⁻¹ day⁻¹ given by continuous infusion) after high-dose chemotherapy (carboplatin 900 mg m⁻² and etoposide 900 mg m⁻²). The patients were not evaluable for a response because we performed consolidated high-dose chemotherapy. However, no evidence of recurrence has been observed 11.8 months (range 2–19) after high-dose chemotherapy. We can conclude that standard dose cisplatin in combination with etoposide or adriamycin and cyclophosphamide plus rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer.     

A Phase I Study of Paclitaxel, Doxorubicin, and Cisplatin in Patients with Previously Untreated Epithelial Ovarian Cancer

Objective.Although doxorubicin is not currently popular as a primary agent in ovarian cancer, overviews of previous studies suggest that the inclusion of doxorubicin may have improved outcome. The purpose of this phase I study was to determine the maximal dose of doxorubicin that could be added to standard doses of paclitaxel and cisplatin with G-CSF support.Methods.Women with FIGO stage III or IV epithelial ovarian cancer were primarily treated with escalating doses of doxorubicin in combination with paclitaxel (135 mg/m²over 24 h) and cisplatin (75 mg/m²) every 3 weeks. Doxorubicin was started at 30 mg/m²and escalated by 10 mg/m²per treatment level. All patients received G-CSF support.Results.Eleven patients were treated at two dose levels. Dose limiting toxicity (DLT) was reached at the 40 mg/m²dose of doxorubicin. All patients experienced grade 4 neutropenia although none required hospitalization. DLT included renal toxicity and prolonged thrombocytopenia. Despite vigorous antiemetic regimens 60% of patients experienced severe nausea and vomiting. Nine patients were assessable for response. Eight patients have had a complete clinical response (89%). Of the five patients undergoing second-look laparotomy two were negative.Conclusions.The maximum tolerated dose of doxorubicin in this three-drug regimen is 30 mg/m²with standard doses of paclitaxel and cisplatin. Hematologic toxicity is manageable using G-CSF. Doxorubicin appears to increase the renal toxicity of cisplatin which may be exaggerated by marked nausea and vomiting. This is an active but toxic regimen and alternative sequences and strategies should be evaluated.     

Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: A randomized, double-blind, placebo-controlled trial

OBJECTIVE: Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor.STUDY DESIGN: A randomized, double-blind, a placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score ≤6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E₂ gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring.RESULTS: The median interval from randomization to delivery was 4 days in the prostaglandin E₂ group (range 0 to 28 days) and versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E₂ group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 ± 1.0 weeks vs 40.5 ± 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E₂-treated patient, but no intervention was required.CONCLUSIONS: Outpatient low-dose prostaglandin E₂ gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring.     

Randomized prospective trial of 5 versus 10 cycles of cyclophosphamide, doxorubicin, and cisplatin in advanced ovarian carcinoma

Five versus ten cycles of cyclophosphamide, doxorubicin, and cisplatin (CAP) were compared in advanced ovarian carcinoma by a prospective randomized study of 78 patients, 41 receiving 5 cycles (CAP5) and 37 receiving 10 cycles (CAP10) of chemotherapy. Patients were stratified by histologic grade and size of residual disease. Cyclophosphamide, 600 mg/m2, doxorubicin, 40 mg/m2, and cisplatin, 100 mg/m2, were administered every 4 weeks for 5 or 10 cycles. Second-look laparotomy was performed to evaluate response and plan further therapy. CAP5 patients found a second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP. CAP10 was more toxic than CAP5 with respect to myelosuppression, hospital admissions for nadir fever, median elevation of creatinine, and degree of peripheral neuropathy. Median follow-up is 64 months. CAP5 and CAP10 were equivalent in surgically documented complete responses (34 versus 35%) and survival (P = 0.41). Twelve partial responders to CAP5 received additional CAP chemotherapy; one complete response resulted. We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic.