Preliminary results of concurrent radiotherapy and chemotherapy in advanced cervical carcinoma: a phase I-II prospective intergroup NCOG-RTOG Study

Thirty-eight patients with advanced carcinoma of the cervix were prospectively treated with a concurrent combination of radiotherapy (RT) and chemotherapy (CT) using the drugs 5-fluorouracil (5FU), mitomycin C and cis-platinum as part of a Northern California Oncology Group (NCOG) and Radiation Therapy Oncology Group (RTOG) intergroup study. RT consisted of 36.00 Gy to the pelvis in 4 weeks followed by a 9.00-Gy parametrial boost. This was followed by two intracavitary applications for a total of 4000 mg hr of radium equivalent when possible. 5FU (1000 mg/m2/24 hr for 96 hr by iv infusion) and mitomycin C (10 mg/m2/iv bolus) were given during the second week of external RT. 5FU (dose as above) and cis-platinum (75 mg/m2/iv over 6 hr) were given during the first intracavitary application. Of 36 patients evaluable for toxicity, 11% had grade 3 nonhematological toxicity and 11% had reversible grade 4 hematological toxicity. There were no toxic deaths. A complete response rate of 62.5% was obtained overall (median survival not reached). This study suggests that this particular combination of RT and CT in advanced cervical carcinoma is effective and well tolerated.     

A case of stage-IVb cervical adenocarcinoma successfully treated by combination chemotherapy: case report

A 54-year-old patient with a Stage IVb adenocarcinoma of the cervix was treated with combination chemotherapy. This regimen consisted of intravenous cisplatin (70 mg/m2) and aclacinomycin A (30 mg/m2) on Day 1, followed by mitomycin C (5 mg/m2) on Day 2 and 3. A pathologically complete response was achieved by this regimen. The patient is well and has been free of symptoms for 66 months.     

Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy

Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.     

CDDP-ACR treatment in patients with recurrent ovarian cancer with prior chemotherapy containing CDDP--a preliminary study of a 14-day continuous infusion of CDDP with ACR

Six patients with recurrent ovarian cancer who had prior chemotherapy were studied for the clinical efficacy of CDDP-ACR treatment. Five out of the 6 had received CDDP a total doses of 1,320, 780, 750, 475, and 340 mg. CDDP-ACR therapy consisted of continuous infusion of CDDP at a daily dose of 10 mg/m2 over 14 days (total CDDP doses; 140 mg/m2) and of intermittent infusion of ACR (aclarubicin) at a dose of 20 mg/body every other day (total ACR doses: 140 mg). There were one CR and five PR and a response rate up to 100% was noted. Toxicity was manifested in slight nausea or vomiting, but there was no nephrotoxicity. However bone marrow was severe. Thrombocytopenia less than 50,000/mcl in 4 pts (67%) and leukopenia less than 1,000 mcl in 3 pts (50%). The mean filterable platinum exposure measured by area under the concentration-time curve (AUC) was as high as 19.7 +/- 6/0 mg.hr/ml. In conclusion the bone marrow toxicity in this regimen was severe, but the therapeutic efficacy was promising. Further studies on the appropriate infusion time and the minimum effective dose of CDDP are needed.     

Cyclic high dose CAP therapy by short-stay admission for ovarian malignancies--to increase total dose of CDDP and to improve quality of life of patients

Since 1986, attempts have been made to improve the anti-cancer effect of Cisplatin (CDDP) in malignant ovarian tumor patients and their quality of life (QOL), by increasing single and total dose of CDDP and by short-stay cyclic treatment at our institution. In this study, the side effects of CDDP at high and low doses were compared and the effect on the QOL was analysed. Twenty ovarian malignant tumor patients who underwent adjuvant chemotherapy (CDDP 70 mg/m2, Adriamycin (ADR) 20 mg/m2, Cyclophosphamide (CPM) 200 mg/m2 given every 4 weeks for a total of 5 times and every 8-12 weeks thereafter for 5 times) after initial surgery were compared with non randomized control patients who received the old regimen of of our institution (CDDP 35 mg/m2, ADR 20 mg/m2, CRP 200 mg/m2, 5-FU 150 mg/m2 for 5 days given every 4 weeks for a total of 5 times without discharge from hospital). There was no significant difference between the groups in the white blood cell (WBC) count and creatinine clearance (Ccr) throughout the treatment, although a slight drop was observed after the second course in both groups. The QOL was examined by interviewing the patients on their physical and mental condition. Although the total amount of CDDP was increased from 175 mg/m2 to as much as 700 mg/m2, no severe nephrotoxicity or myelosuppression was seen and patients felt better and preserved a good QOL during a short hospital stay. These results clearly indicate the efficacy of our new regimen.     

Concurrent chemoradiation in advanced cervical cancer

The pelvis is the predominant site of failure following radical radiotherapy (RT) for locally advanced cervical cancer. We report the results of phase I-II studies on 200 patients with bulky (greater than or equal to 5 cm) carcinoma of the cervix. Patients were treated between 1981 and 1988 on sequential protocols of concurrent chemoradiation to establish an acceptable treatment regimen. RT with daily or partially hyperfractionated pelvic (n = 154) or pelvic plus paraaortic (n = 46) fields was given by continuous (n = 154) or split course (n = 46) regimens. Infusional fluorouracil (5-FU) in a dose of 1 g/m2/day was given on the first and last 4 days of a 5-week course of continuous RT, or with both halves of split course RT. Seventy-eight patients received bolus mitomycin C (Mit-C), 6 mg/m2, once or twice with the start of the 5-FU infusion. The median external RT dose was 46 Gy (range 40 to 65 Gy) followed in 90% (n = 181) by a single intracavitary application of 40 Gy using a linear source of cesium-137. Median follow up is 2.5 years (range 0.6 to 6.9 years) and is sufficient to reliably estimate late toxicities. Acute toxicities were transient oral mucositis (13), RT interruption for enteritis (7), febrile neutropenia (3), and thrombocytopenic tumor bleed (1). Serious late toxicities resulted in death in 3 patients and occurred in bladder in 6 and in bowel in 25, including 8 patients with tumor recurrence. The incidence of late bowel toxicity correlated with the specific therapy given and decreased with each successive protocol. On logistic regression the only treatment variable showing a statistically significant effect on complications was the use of Mit-C (P = 0.0053). Pelvic RT and 5-FU alone produced fewer complications, only 4/105, than historically seen with standard pelvic RT alone. Three-year pelvic control and survival rates were 85 and 71% respectively in stage Ib/II (n = 100) and 50 and 42% in stage III/IV (n = 100). Encouraged by these results and decreased toxicity, we have begun a phase III study to determine whether the addition of concurrent 5-FU to continuous partially hyperfractionated pelvic RT improves local control and survival.     

Preventive effect of urinastatin on cisplatin-induced nephrotoxicity

Anticancer chemotherapy with cisplatin (CDD) as the main drug (combined with adriamycin (ADM) and cyclophosphamide (CPM), PAC therapy) was performed on patients with ovarian cancer. Urinastatin (US) was concurrently administered to assess its effectiveness in preventing CDDP-induced nephrotoxicity. Twenty-two patients with gynecological malignant tumor were treated with PAC therapy, and of these, twelve concurrently received US. The ten who did not receive US served as the control. As a rule, one course of PAC therapy consisted of 50mg/m2 CDDP, 50mg/m2 ADM and 500mg/m2 CPM. Before the administration of CDDP, US 100,000 units was administered by I.V. drip infusion and after the administration, US 400,000 units was again administered by I.V. drip infusion at a speed of 100,000 to 200,000 units/hour. A total of approximately 3,500ml of fluids was administered I.V.. Each course of PAC therapy took 7 to 14 hours to complete. The control group underwent PAC therapy in a regimen not including US. As indexes of nephrotoxicity, serum levels of BUN, creatinine (Cr), and creatinine clearance (Ccr), and N-acetyl-beta-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP), and arylamidase (AA) activity in the urine was determined before treatment and at days 1, 2, 3, 7, 14, and 21 after the initiation of PAC therapy. Changes in serum BUN, Cr, and Ccr levels after CDDP administration in the group with and the group without concurrent US were similar. Urinary gamma-GTP, AA, and NAG activity remained unchanged after CDDP administration in the group with concurrent US. In contrast, in the group without US, this urinary enzyme activity was transiently increased after CDDP administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of effect from mitomycin c plus 5-fluorouracil in platin-resistant ovarian cancer: a phase II study

Sixteen patients with advanced ovarian cancer were included in a phase II study with mitomycin c (MMC) plus 5-fluorouracil (5-FU). All patients had previously received platin-based combination therapy, but were resistant to this treatment. A MMC 10 mg m⁻² intravenous (iv) bolus was given on day 1 every 6 weeks, and 5-FU 1000 mg m⁻² was given iv on days 1–3 every 3 weeks, as a continuous infusion over 72 h. Fifteen patients were evaluable for response. There were no responders, neither partial nor complete. The median survival was 6 months. The toxicity was primarily bone marrow suppression. The treatment was generally well tolerated. No patients had grade 4 toxicity and only five had grade 3 hematologic toxicity. In conclusion, we find the present regimen to be ineffective in the treatment of platin-resistant ovarian cancer.     

Menstrual and Hormone Patterns in Women Treated with High-Dose Cisplatin and Bleomycin

Menstrual and hormone patterns were investigated in 10 fertile women (median age 37, range 25-43 years) with locally advanced cervical cancer treated with neoadjuvant chemotherapy (CT). CT consisted of two cycles of high-dose cisplatin (CDDP, 40 mg/m², Days 1 to 4) and bleomycin (B, 15 mg/m², Days 1 and 8) separated by an interval of 21 days. Menstrual patterns before and during CT were recorded. FSH, LH, estradiol, and progesterone were assayed on the day that treatment was begun, after 2 and 4 days of CDDP administration, and weekly between and after the two cycles. Hormone assays during the first week of CT showed no significant change in hormone levels. After the first course of CT, five patients showed hypergonadotrophic amenorrhea and five patients maintained menses, two showing ovulatory and three showing follicular phase hormone patterns. After the second course of CT, one more patient become amenorrheic, and endocrine follow-up showed that two patients maintained hypergonadotrophic amenorrhea, four with hypergonadotrophic amenorrhea had a return of hormone levels to the follicular range of 7-9 weeks after, three maintained follicular phase hormone patterns until operation, and one ovulated. Gonadal dysfunction should be included among the side effects of high-dose CDDP and B regimens.     

cis-platinum as adjunctive to surgery in early stage ovarian carcinoma: Effects on lymphoid cell subpopulations

The effect of single-drug cis-diamminedichloroplatinum (CDDP) treatment on the distribution of T-lymphocyte subsets and monocytes was determined using monoclonal antibodies and a flow cytometry technique. Thirty-nine patients with radically operated ovarian carcinoma received postoperative treatment with six cycles of CDDP 50 mg/m2, and were examined either before, during, or after chemotherapy. During treatment, the number of OKT4+ (mainly T-helper) cells was reduced, whereas the number of OKT8+ (mainly T-suppressor/cytotoxic) cells was increased. Four to six months after the CDDP treatment was ended, these aberrations were no longer seen. The number of 1D5+ cells (monocytes) was not influenced by the treatment. It is concluded that no long-lasting change in the distribution of immunocompetent cells could be detected after this regimen of CDDP treatment.     

Quantitative evaluation for murine oocyte toxicity following intraperitoneal treatment with chemotherapeutic agents

The ovarian toxicity induced with 12 oncostatics was evaluated using syngeneic mice, 6-week-old C57BL/6. Each drug diluted with saline to 0.2ml was intraperitoneally infused twice at 6 and 7 weeks old. Mice were sacrificed 2 weeks after the second treatment, the ovaries removed and fixed for serial sectioning, and the small oocytes of Pedersen and Peters counted. Small oocytes were destroyed in a dose-dependent fashion, and ED50, an effective dose of which produced 50% destruction of small oocytes in each mice group, was significantly divided into 4 groups of statistical difference (F = 5.77, p less than 0.0213). The smallest dose of ED50 (mg/mouse) (the strongest in oocyte toxicity): Actinomycin D 0.0064, doxorubicin 0.0184, peplomycin 0.021; the second: Bleomycin 0.107, mitomycin 0.0707, CDDP 0.120; the third: Cyclophosphamide 0.427; and the largest (the weakest): Ifosphamide 3.01, 5FU 6.17, etoposide 6.11, methotrexate 2.0 much less than, vinblastine 0.1 much less than. The most toxic included those which could attack not only DNA, but also RNA biosynthesis and the least included those which could have an effect on enzymes or proteins with no direct action on DNA. The ratio of ED50 to HUD, the single usual dose for human cancer chemotherapy, were smallest for doxorubicin (2.23), cyclophosphamide (2.59) and CDDP (5.19). Although these three are very useful oncostatics for ovarian cancer, they might have serious potential toxicity for human ovarian oocytes.     

Matched unrelated donor bone marrow transplantation for the treatment of platinum refractory ovarian carcinoma: a case report

BACKGROUND: We are reporting on a case of platinum-refractory low-grade ovarian cancer responding to treatment with an allogeneic bone marrow transplantation from an unrelated donor. CASE: The 37-year-old patient received a preparative regimen consisting of fludarabine 25 mg/m(2) on days -6, -5, -4, -3 and -2, melphalan 70 mg/m(2) on days -3 and -2, and thymoglobulin 2 mg/kg on days -3, -2 and -1. An unrelated HLA-compatible bone marrow was infused on day 0. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. The patient demonstrated complete donor chimerism. Serial CT scans of the abdomen and pelvis over the following 15 months showed a slow regression of the malignant lesion. CONCLUSION: Engraftment of an unrelated donor marrow was achieved in a patient with ovarian cancer and induced a tumor response. This suggests the presence of a graft-versus-tumor effect in ovarian cancer. Further study is underway.     

Rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial

OBJECTIVE: To retrospectively analyze data from a previously reported randomized trial of either pelvic radiation (RT) or RT + chemotherapy (CT) in patients undergoing radical hysterectomy and pelvic lymphadenectomy with positive pelvic lymph nodes, parametrial involvement, or surgical margins; to explore associations between RT + CT; and to investigate histopathologic and clinical factors which might be predictive of recurrence. METHODS: Histopathologic sections from biopsies and hysterectomies and clinical data were reviewed from patients with stage IA2, IB, or IIA cervical cancer treated with RT or RT + CT (cisplatin 70 mg/m2 plus fluorouracil 1000 mg/m2 every 3 weeks for four cycles). A univariate analysis was performed because the relatively small sample size limited the interpretation of a multivariate analysis. RESULTS: Of the 268 enrolled women, 243 (RT = 116; RT + CT = 127) were evaluable. The beneficial effect of adjuvant CT was not strongly associated with patient age, histological type, or tumor grade. The prognostic significance of histological type, tumor size, number of positive nodes, and parametrial extension in the RT group was less apparent when CT was added. The absolute improvement in 5-year survival for adjuvant CT in patients with tumors < or =2 cm was only 5% (77% versus 82%), while for those with tumors >2 cm it was 19% (58% versus 77%). Similarly, the absolute 5-year survival benefit was less evident among patients with one nodal metastasis (79% versus 83%) than when at least two nodes were positive (55% versus 75%). CONCLUSIONS: In this exploratory, hypothesis-generating analysis, adding CT to RT after radical hysterectomy, appears to provide a smaller absolute benefit when only one node is positive or when the tumor size is < 2 cm. Further study of the role of CT after radical hysterectomy in patients with a low risk of recurrence may be warranted.     

Mature Results of a Phase II Trial of Concomitant Cisplatin/Pelvic Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Cervix

Purpose:Patients with locally advanced squamous cell carcinoma of the cervix have a poor prognosis when treated by standard ratiotherapy (RT) alone. Factors such as large tumor volume or nodal disease result in pelvic and distant treatment failures. Cisplatin (CDDP), a known radiosensitizer with documented activity in squamous cell carcinomas, was used in a phase II prospective study to evaluate the efficacy of combined chemo/radiotherapy in locally advanced squamous cell carcinomas of the cervix.Method:CDDP was administered (20 mg/m²) daily × 5 at 21-day intervals with concomitant external beam and intracavity RT. Standard RT was delivered at 1.8–2.0 Gy/day, 5 fractions per week for 5 weeks. Intracavitary cesium insertions were planned to treat point A to approximately 80 Gy.Results:Fifty-nine patients were enrolled from March 1986 to July 1990. Four patients were voluntarily withdrawn, leaving 55 patients evaluable for response. Of these, 16 were Stage IB/IIA, 11 were Stage IIB, 24 were Stage III, and 4 were Stage IV. The median age of patients enrolled was 47 years (range 27–79). Median follow-up time was 65 months (range 60–113). Histopathologic confirmation of node status was available in 33 patients, of whom 45.5% (15/33) had nodal metastases. Overall response was 96% (CR = 87%, PR = 9.0%) and 3.6% had progressive disease during treatment. Forty-six patients were evaluable at 5 years for overall and disease-free survival. Calculations were based on Kaplan–Meier product limit estimates. The 5-year survival was 73% for Stage IB/IIA, 60% for Stage IIB, 67% for Stage III, and 25% for Stage IV. The disease-free survival at 5 years was 73% for Stage for IB/IIA, 50% for Stage IIB, 67% for Stage III, and 25% for Stage IV. Hematologic toxicity was severe but tolerable. No treatment-related deaths occurred.Conclusion:Concomitant CDDP/RT is a safe and tolerable method of treating patients with locally advanced squamous cell carcinoma of the cervix. Our data suggest a benefit in both disease-free and 5-year survival, particularly notable among patients with Stage III disease.     

Cisplatin/5-Fluorouracil Treatment of Recurrent Cervical Carcinoma: A Phase II Study with Long-Term Follow-up

Objective: To evaluate the response rate and corrected survival in patients with recurrent cervical carcinoma (RCC) treated with 100 mg/m²cisplatin (CDDP) iv on Day 1 and 1000 mg/m²5-fluorouracil (5-FU) iv on Days 1 to 5. Methods: A phase II study of CDDP/5-FU in RCC was initiated in 1986. Up to December 1991, a total of 72 patients were enrolled. Of these, 65 were evaluable for response. Results: The overall response rate was 49%. For 9 patients with complete remission, the median duration of response was 16 months, range 6 to 79+. The corresponding figures for 26 patients with partial remission were 10 months, range 3 to 80 months. By multivariate analysis, FIGO stage, disease-free interval, WHO performance status, and number of lesions at recurrence were independent prognostic variables. Twenty-two percent of the patients survived for more than 2 years and 9% for more than 5 years. Toxicity was tolerable. Leucopenia, ototoxicity, and neurotoxicity were the main problems. Conclusion: A high response rate (49%) was observed with CDDP/5-FU treatment in patients with RCC with 9% of the patients surviving for more than 5 years.     

The use of concomitant chemotherapy and radiotherapy prior to surgery in advanced stage carcinoma of the vulva

Six cases of primary advanced squamous carcinoma of the vulva were treated with concomitant chemotherapy and radiotherapy (C + RT). In five patients it was given in preparation for surgery. The radiation was delivered to the whole pelvis in 10 equal daily fractions of either 2.0 or 2.5 Gy. Mitomycin C (10 mg/m2) was given on Day 1, and 5-fluorouracil (1,000 mg/m2) was given daily from Days 1 to 4, inclusive. All six patients had satisfactory early tumor response. Three patients received one course of C + RT and three were given two courses. One patient died suddenly of unknown causes 6 days after completing the C + RT. One patient with fixed groin nodes was treated with palliative intent. She maintained a complete local response but died 6 months later of liver metastases. The remaining four patients underwent surgery without healing complications and are alive with no evidence of disease at 1, 4, 14, and 26 months. In our experience vulval carcinomas can be reduced in size and extent by prior chemotherapy and radiotherapy and require less extensive surgery.     

A pilot study of chemo-radiotherapy in advanced carcinoma of the vulva

Advanced squamous cell carcinoma of the vulva (FIGO stages III and IV) has a poor cure rate even with exenterative surgery. We report a pilot study of combined pre-operative chemo-radiotherapy (CHT/RT) in all patients with advanced vulval carcinoma presenting to St Bartholomew's Hospital between July 1987 and March 1989. Twelve patients have been treated, of whom nine had primary lesions (four FIGO stage III and five stage IV) and three had recurrent disease after simple or radical vulvectomy. Seven patients were treated with an initial split course of CHT/RT: there was one treatment-related death and the others have all died following recurrence with a median disease-free survival of 5 months (range 3-12) and a median survival of 7 months (range 3-16). Five patients have received a continuous course of CHT/RT: one died before operation with pulmonary metastases, three patients are disease free at 6 to 9 months, and another patient has been treated with only palliative intent. Toxicity was acceptable in the continuous regimen and this treatment seems to have a promising role in the management of advanced carcinoma of the vulva. A review of the literature on combined therapy is presented.     

A pilot study of chemo-radiotherapy in advanced carcinoma of the vulva

Summary. Advanced squamous cell carcinoma of the vulva (FIGO stages III and IV) has a poor cure rate even with exenterative surgery. We report a pilot study of combined pre-operative chemo-radiotherapy (CHT/RT) in all patients with advanced vulval carcinoma presenting to St Bartholomew's Hospital between July 1987 and March 1989. Twelve patients have been treated, of whom nine had primary lesions (four FIGO stage III and five stage IV) and three had recurrent disease after simple or radical vulvectomy. Seven patients were treated with an initial split course of CHT/RT: there was one treatment-related death and the others have all died following recurrence with a median disease-free survival of 5 months (range 3–12) and a median survival of 7 months (range 3-16). Five patients have received a continuous course of CHT/RT: one died before operation with pulmonary metastases, three patients are disease free at 6 to 9 months, and another patient has been treated with only palliative intent. Toxicity was acceptable in the continuous regimen and this treatment seems to have a promising role in the management of advanced carcinoma of the vulva. A review of the literature on combined therapy is presented.     

Concurrent radiotherapy and weekly paclitaxel for locally advanced or recurrent squamous cell carcinoma of the uterine cervix. A pilot study with intensification of dose

OBJECTIVE: This study included patients with inoperable primary or recurrent cervical cancer whose treatment plan called for exclusive radiotherapy. The endopoints of the study were to confirm the feasibility of concurrent radiotherapy and paclitaxel in relation to potential acute toxicity and to evaluate if an increase of complete local control might be obtained with the association of paclitaxel to radiotherapy as a radiosensitizer. METHODS: Twenty patients (13 new cases, stage IIB-III, and 7 with pelvic recurrences) were enrolled and, with exclusion of one recurrence, 19 were evaluable for acute toxicity and response. In new cases, radiotherapy was conventionally administered: 50.4 Gy/28 fractions by external beam (whole pelvis) followed by intracavitary cesium or reduced transcutaneous field. In recurrences, radiotherapy was performed with external beam only through individualized fields. Paclitaxel was administered weekly at the dose of 40 mg/m2 or 60 mg/m2 during the entire course of external radiotherapy. RESULTS: Complete regression (CR) as defined by clinical and imaging examinations was achieved in eight of the 13 new cases (62%) and in four of the six recurrences (66%), for a total complete response rate equal to 63%. Five patients (3 treated with 40 mg/m2 and 2 with 60 mg/m2) experienced grade 3 small bowel toxicity, one patient treated with 40 mg/m2 grade 3 bladder toxicity and one patient treated with 60 mg/m2 had grade 4 mucositis. Out of 12 CR patients at the end of treatment, ten maintain complete local remission for a median follow-up of 47 months but two have developed distant metastases. CONCLUSION: The results confirm that this approach is feasible and suggest the use of paclitaxel as radiosensitizer in locally advanced cervical cancer.     

The prevention of CDDP-induced emesis with a combination regimen including metoclopramide, dexamethasone, droperidol and diphenhydramine

The dose limiting factors of cisplatinum are nephrotoxicity and emesis. Nephrotoxicity has been reduced by hydration but nausea and vomiting caused by cisplatinum have led to refusal of potentially curative therapy by a number of patients. The prevention of nausea and vomiting by a combination of antiemetic drugs administered to ovarian patients receiving chemotherapy inducing (cisplatinum 50mg/m2, adriamycin 300 mg/m2, cyclophosphamide 300 mg/m2 and 5FU 350 mg/m2) was studied. the combination antiemetic drugs were metoclopramide (1mg/kg), dexamethasone (10mg/m2), droperidol (1mg/m2) and diphenhydramine (20mg/body). These drugs without diphenhydramine were administered intravenously 30 minutes before and 2.5 hours, 5 hours and 7.5 hours after chemotherapy. Diphenhydramine was administered intramuscularly 30 minutes before and 5 hours after chemotherapy. No vomiting was noted in 82.6% (19/23) of cases, and no patient vomited more than four times. This combination regimen provided very good protection against cisplatinum induced emesis.