Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.

PURPOSE: To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer. PATIENTS AND METHODS: Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles. RESULTS: A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF. CONCLUSION: This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.

High doses of 5-fluorouracil and epirubicin with or without cisplatin in advanced gastric cancer: a randomized study.

BACKGROUND: A prospective randomized clinical study was performed in patients with locally advanced or metastatic gastric cancer. The purpose of the study was to determine the activity of high doses of 5-fluorouracil and epirubicin (FE) vs. the same combination + cisplatin (FEP), and particularly the value of cisplatin in the combination. PATIENTS AND METHODS: A total of 122 patients was included in the study; 110 of them were assessable. In the FE arm, the treatment involved 1000 mg/m2 in a 6-hr infusion of 5-fluorouracil on days 1, 2, 3, 4 and 5 and 120 mg/m2 of epirubicin i.v. on day 1. In the FEP arm, the same combination of cytostatics + cisplatin (30 mg/m2) was administered on days 2 and 4. The cycles were repeated after 4 weeks. Altogether, 468 cycles of chemotherapy were given (FE, 240; FEP, 228). RESULTS: In the FE arm, 56 patients were assessable, with 2 complete and 14 partial remissions (28.6%); in the FEP arm, 4 complete and 19 partial remissions (42.6%) were observed in 54 assessable patients. Median survival in the FE group was 7.1 months and in the FEP group 9.6 months. The survival difference was statistically significant (Cox's test, P<0.05). The most frequent side effects included grade 2 and 3 alopecia (FE, 93%; FEP, 94%) and grade 2 and 3 vomiting (FE, 20%; FEP, 35%). Grade 3 and 4 leukopenia was observed in 9% of patients in the FE group and in 13% of patients in the FEP group, with 6 cases of febrile neutropenia (FE, 4%; FEP, 7%). Stenocardia was registered in 1 patient in the FE group and in 2 patients in the FEP group. No treatment-related death was registered. CONCLUSIONS: The addition of cisplatin to high doses of 5-fluorouracil and epirubicin resulted in a statistically significant better survival of treated patients.

A phase II trial of cardioprotection with Cardioxane (ICRF-187) in patients with advanced breast cancer receiving 5-fluorouracil, doxorubicin and cyclophosphamide.

From January 1991 to August 1993, 237 women with metastatic breast cancer were recruited into a multicentric phase II clinical trial designed to assess the cardioprotective activity of Cardioxane (ICRF-187). All patients were treated with 5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (FDC) and Cardioxane 1000 mg/m2, in cycles repeated every 3-4 weeks. Cardiac functions were assessed at baseline by physical examination, ECG, and resting ultrasound left ventricle ejection fraction (LVEF). The same tests were repeated regularly after the 3rd, 6th, 8th cycle and every additional 100 mg/m2 of doxorubicin. At the end of the study there were 212 evaluable patients. Prior to analysis, patients were stratified according to the presence of cardiac risks at study entry. One hundred thirty-three patients (63%) bore one or more cardiac risks. The average total cumulative dose of doxorubicin administered to the group was 311 mg/m2 (range: 200-900 mg/m2). Overall response (CR + PR) was 49.5% (105/212), with 12% of patients entering complete remission. General toxicity (WHO grading) was mild and tolerable; no excessive myelosuppression or related symptoms were observed. Three patients from the risk group experienced cardiotoxicity, with an LVEF fall below 45%, and had to be removed from the study. Another 3 patients (1 from the risk group) were removed from the study due to clinically documented congestive heart failure after 200, 300 and 400 mg/m2 of doxorubicin. In our study, Cardioxane (ICRF-187) did not influence the antitumor efficacy of FDC chemotherapy, nor did concomitant administration of Cardioxane and chemotherapy result in any other or severer toxicity than that already known for this regimen. Finally, the observation that 51% of patients with preexisting cardiac risks received doxorubicin at dose range of 450-900 mg/m2 without significant clinical or laboratory signs of cardiotoxicity supports the evidence that Cardioxane provided cardiac protection offering the possibility of longer doxorubicin chemotherapy.

Combination of 5-fluorouracil, imidazole carboxamide, BCNU and prednisolone (FIB-P) as a salvage chemotherapy in heavily pretreated breast cancer patients.

The results of treatment with 5-fluorouracil, imidazole carboxamide, BCNU and prednisolone (FIB-P) salvage chemotherapy in 60 patients with heavily pretreated advanced breast cancer are presented. For most of the patients (82%) this was the third line of chemotherapy. Performance status (ECOG) was 1, 2 and 3 in respectively 13, 27, and 20 patients. Predominant metastatic sites were: soft tissue (3/60, 5%), bone (22/60, 37%), and viscera (35/60, 58%). Tumor burden (number of affected organic systems) was 1, 2 and 3 or more in respectively 18, 24 and 16 patients. Average dose intensity received was 0.74 (range, 0.47-0.98); the average number of cycles was 3.8 (range, 2-8). Objective response (CR + PR) was observed in 22 patients (1 CR, 21 PR), with a response rate of 37% (22/60). Median duration of remission was 7 months (range, 3-15). Tumor burden was the only pretreatment patient characteristic that significantly influenced the remission rate (p less than 0.10). Dose intensity significantly affected tumor response (p less than 0.05). Toxic side effects (gastrointestinal disorders, alopecia and myelotoxicity) were generally moderate and tolerable. No treatment-related death occurred. FIB-P proved to be an active salvage chemotherapy in heavily pretreated patients with advanced breast cancer.

Randomized phase II trial of high-dose 4'-epi-doxorubicin + cyclophosphamide versus high-dose 4'-epi-doxorubicin + cisplatin in previously untreated patients with extensive small cell lung cancer.

One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin (120 mg/m2) in combination with either cyclophosphamide (800 mg/m2; arm 1) or cisplatin (60 mg/m2; arm 2). Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only. The overall response rate (CR+PR) in arm 1 and 2 were 61.4 (27/44) and 67.3% (35/52), respectively. The mean duration of remission was 4.4 months (arm 1) and 4.9 months (arm 2). The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient's death was observed in arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.

Carboplatin activity in untreated metastatic breast cancer patients--results of a phase II study.

Due to the favourable results previously obtained with cisplatin in breast cancer (54% response rate), we studied a second-generation platinum analogue, carboplatin, in patients with previously untreated breast cancer. A total of 20 patients were entered in the study and all were evaluable. The median age was 57 years and all patients were in menopause. Karnofsky scores of 80-100 and 40-70 were registered in 14 and 6 cases, respectively. The predominant metastatic site was soft tissue in 12 subjects, visceral organs in 5 and bone in 3; 14 patients had greater than 2 metastatic sites. Carboplatin was given i.v. at a dose of 400 mg/m2 on day 1, with a 3-week rest period. In 13 patients who did not respond or whose disease recurred after carboplatin treatment, the CMFVP, CAP or FAC regimen was given as second line treatment. Carboplatin activity was observed in 4 patients [2 complete remissions (CRs) and 2 partial responses (PRs)], for a response rate of 20% (4/20); the 2 PRs were observed in soft tissue and bone and the 2 CRs, in lung, liver and bone. Remission lasted 2-10 months (mean, 4 months). CMFVP given as second-line chemotherapy to 13 patients produced 7 PRs (7/13, 54%). Toxicity was moderate, producing no drug-related deaths. Anemia (grade I-II) was recorded in seven patients; grade I-II leukopenia, in six; and grade III-IV leukopenia in two (median leukocyte nadir, 1,600/mm3). Thrombocytopenia was observed in three cases (grades I, II and III; median platelet nadir, 47,800/mm3). Unpleasant nausea/vomiting was pronounced (12 cases of grade III-IV) in 19 subjects. There were no cases of neuro- or nephrotoxicity. Due to permanent myelosuppression, no more than five cycles could be given. Our study showed that, unlike cisplatin, carboplatin given at a dose of 400 mg/m2 has low antitumorigenic activity in breast cancer patients and produces pronounced myelotoxicity. Additional first-line chemotherapy studies using carboplatin are needed to define the antitumorigenic activity of this platinum analogue.

Combination of idarubicin and cyclophosphamide administered orally in untreated postmenopausal breast cancer patients. A phase II study.

On the basis of results obtained with oral idarubicin administration in breast cancer, which have shown an established antitumor activity in approximately 28% of cases, this compound was combined with cyclophosphamide (also given orally) in postmenopausal patients with an unknown or negative steroid receptor status. The study comprised 45 untreated patients out of which 44 were evaluable for response and toxicity. The mean age was 62.5 years (range 51-75). The majority of patients had soft tissue (24) and visceral organ (17) metastases. Idarubicin was administered in one oral daily dose of 45 mg/m2 on day 1; the oral cyclophosphamide dose was 200 mg/m2 daily on days 3, 4, 5 and 6. An objective response to treatment was observed in 41% of patients (18/44, 95% confidence interval 28-56%). Complete remission (lung) was observed in 2 patients (5%), while 16 patients achieved a partial response. Eleven patients showed no change, while 15 patients progressed. A particularly good response was obtained in soft tissue metastases (54%, 13/24) while in visceral organs a response was achieved in 31% of patients (5/16). The remissions lasted 2-14 months (median 7 months), and median survival was 14+ months. Toxicity was mild and the treatment well tolerated. Grade I/II leukopenia was observed in 24% of patients (median WBC nadir 3,100); there were no signs of cardiotoxicity. Grade I and II alopecia was observed in 75% of patients: nausea/vomiting were present in 73% of cases. The results of this study indicate that oral administration of idarubicin and cyclophosphamide produces a valuable antitumorigenic effect in postmenopausal breast cancer patients, particularly in soft tissue metastases. Further randomized studies will be needed to evaluate this treatment approach.

cis-platinum-based alternating non-cross-resistant chemotherapy as a first-line treatment in metastatic breast cancer. A phase II study.

Exposure to multiple non-cross-resistant drugs should increase cell kill and the chance of achieving more complete and partial responses. Our earlier study in breast cancer showed that second-line CAP (cyclophosphamide, adriamycin, cis-platinum) treatment was not cross-resistant to the CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone) regimen and produced a 51% response rate. These facts initiated a phase II study which used an alternating CMFVP/CAP regimen. Altogether, 49 patients entered the study and 45 were evaluated (greater than 2 cycles). The CMFVP regimen consisted of cyclophosphamide (200 mg/m2 on days 1, 2, 3, 4 and 5), methotrexate (30 mg/m2 on days 2 and 4), 5-fluorouracil (500 mg/m2 on days 1, 3 and 5), vincristine (1.4 mg/m2 on days 1 and 5), and prednisolone (40 mg p.o. on days 1-5), and was alternated with the CAP schedule (300 mg/m2 cyclophosphamide on days 1, 3 and 5, 50 mg/m2 adriamycin on day 1, and 30 mg/m2 cis-platinum on days 1, 3 and 5). Overall response was high, and 37 patients out of 45 responded (82%), with a 28% CR rate (13/45). A particularly high response rate was observed in soft tissues (86%, 18/21) and visceral organs (84%, 16/19). Only 1 patient progressed (3%). The duration of remission was 4-21+ months (median, 12 months). Six of 13 CR patients were still disease free 15 months after the treatment was stopped. The duration of survival was 5-25+ months (median, 15+ months). Toxicity was moderate (myelosuppression in 53% of patients, mainly grade I-II; stomatitis in 11%, except for 100% alopecia and 90% nausea and vomiting). One drug-related death (bone marrow aplasia) was recorded. The high antitumorigenic activity of the alternating regimen used is encouraging and may call for a randomized study for the ultimate evaluation of this treatment approach.

Open phase II with 5-fluorouracil, 4-epi-doxorubicin and mitomycin C (FEM) in advanced gastric cancer.

Forty-four patients with advanced gastric cancer were treated with a combination including 5-fluorouracil, 4-epi-doxorubicin and mitomycin C. 4-Epi-doxorubicin was substituted for adriamycin in MacDonald's original schedule. The combined treatment involved 600 mg/m2 i.v. of 5-fluorouracil on days 1, 8, 29 and 36; 80 mg/m2 i.v. of 4-epi-doxorubicin on days 1 and 29; and 10 g/m2 i.v. of mitomycin C on day 1. The cycle was repeated on day 57 after the start of treatment. Out of 44 patients, 39 were evaluable. Thirteen partial remissions (33%) were achieved. The average duration of remission was 7 months (range, 3-12 months). The average survival of the responders was 9 months, and that of nonresponders 3.5 months. Toxicity was moderate, well-tolerated and, as compared with the FAM schedule, less pronounced, particularly as regards myelotoxicity. Thus, the substitution of 4-epi-doxorubicin for adriamycin in the original schedule of MacDonald et al. (1980) did not improve treatment results, but the observed toxicity was less pronounced.

Phase II study of 4'-epi-doxorubicin in patients with untreated, extensive small cell lung cancer. South-East European Oncology Group (SEEOG).

The purpose of the study was to investigate the antitumour activity and toxicity of high dose (120 mg m-2) single agent epirubicin therapy in untreated extensive small cell lung cancer patients. Out of 80 patients entered, 71 were evaluable for both antitumour activity and toxicity, 4 only for toxicity and 5 were lost for follow-up. The drug possessed a high antitumour activity, the overall response rate was 47.9% (34/71) with 4 complete remissions (CR) and 30 partial remissions (PR). The median remission duration was 3.5 months. Particular drug activity was observed in the primary tumours, lymph nodes and pleural metastases. Toxicity (leukopenia, anaemia, vomiting, reversible rhythmic cardiac disorder, stomatitis) was mild, alopecia was registered less than in adriamycin medication. One fatal congestive heart failure occurred. The actual mean survival time calculated on the basis of the data gained from 64 patients was 7.0 months (range 2-22). The high antitumour activity and no increase in toxicity justify the incorporation of high dose epirubicin into combination therapy.

Combination of cyclophosphamide, adriamycin and platinum (CAP) versus 5-fluorouracil, adriamycin and cyclophosphamide (FAC) as primary treatment in metastatic breast cancer: results of a prospective randomized study.

Based on favorable results we reported earlier with the CAP regimen in breast cancer (CAP vs CMFVP), the present study compared the CAP with the FAC regimen, which is so far one of the most active adriamycin containing chemotherapy regimens in breast cancer. The aim of the study was to find the optimal first line treatment and possibly evaluate the role of cis platinum in breast cancer chemotherapy. The CAP schedule consisted of cyclophosphamide 200 mg/m2 i.v. days 1, 3 and 5, adriamycin 40 mg/m2 i.v. day 1, and platinum 30 mg/m2 i.v. day 1, 3 and 5. The FAC schedule included 5-FU 500 mg/m2 days 1 and 8, adriamycin 50 mg/m2 day 1, and cyclophosphamide 500 mg/m2 day 1. One hundred and twenty-six previously untreated patients received greater than 2 cycles and were evaluated. In the CAP arm 15 complete (26%) and 24 partial remissions were observed, resulting in a 67% overall response rate (39/58). The response in soft tissue and visceral organs was notable (78% - 22/28, 71% - 15/21) with an important complete response rate (32%). In the FAC arm there was an overall response in 41% (28/68) of patients, with 8 complete (12%) and 20 partial responses. The difference in overall response, complete response, and response in soft tissue and visceral organs, was statistically significant in favor of the CAP arm (P less than 0.005). Concerning bone metastases there was no difference between the two schedules in response rate, nor in the median remission duration (CAP 11, FAC 10 months). In spite of a somewhat longer median survival in the CAP group, the difference (13 months vs 9 months) was not statistically significant (P = 0.10). Toxicity was moderate and tolerable in both regimens with more pronounced myelosuppression and vomiting in the CAP group. Compared with the FAC schedule the platinum containing combination chemotherapy (CAP) showed higher antitumor activity with no reflection on remission duration and survival.

Cytostatic treatment of metastatic cervical carcinoma.

The activity of cytostatics in cervical cancer has not as yet been sufficiently investigated. This is especially true for combined cytostatic treatments. The only two cytostatics that have been adequately examined in clinical trials in a larger number of patients are 5-fluorouracil and cis-dichlorodiamineplatinum. The paper presents the results of treatment with single cytostatic agents and the combinations of different cytostatics, emphasizing the role of combined treatment using irradiation and cytostatics. It also describes the preliminary results of a Phase II trial going on at the Central Institute for Tumors in Zagreb, using a combination of cis-DDP, 5-fluorouracil and vincristine. So far the results of 11 out of 14 patients included in the trial have been evaluated. Objective remission (CR + PR) was achieved in 4 patients (33%). Toxic side-effects were mild and tolerable for the patients. In conclusion, the reasons are given why chemotherapy has not as yet gained a more important place in the treatment of advanced forms of cervical cancer.

[Prevention of extravasation necroses as a complication following intravenous cytostatic drug therapy. Results of an open pilot study]. / Verhinderung von Extravasatnekrosen als Komplikation nach intravenöser Zytostatikatherapie. Ergebnisse einer offenen Pilotstudie.

Extravasation of some cytostatics applied i.v. can often cause local edema with skin redness, thrombophlebitis and not infrequently skin necrosis with chronic ulcera. Local treatment is usually ineffective, and so far surgical excision of ulcera is the only curative approach. Tetrachlorodecaoxygen anion complex (TCDO) has shown high activity in healing chronic leg ulcera, by increasing pO2 in hypoxic wound tissue and stimulating phagocytosis as one of anti-inflammatory processes To study the local activity of TCDO in tissue necrosis and chronic ulcera caused by cytostatic extravasation, 23 patients with local skin complications underwent local treatment with TCDO, made as isotonic water solution. Seventeen patients experienced only local edema with redness, while 6 patients showed deep chronic ulcera. All the skin changes were complications after i.v. doxorubicin, cisplatinum, dactinomycin or vinblastine application. The treatments with TCDO followed 1-3 months after ulcera appeared, while skin inflammations were treated 1-8 days after they occurred. TCDO was applied locally twice a day by impregnated cotton tissue for 4-6 weeks. Evaluable were only measurable lesions. From 17 patients with only skin inflammation 3 patients obtained complete resolution, 8 partial resolution and 6 had stable lesions. Thus, overall response was recorded in 65% of patients (11/17). In 6 patients with deep chronic ulcera a longer treatment (6 weeks) was needed, and in 5 of them the complete epithelization and resolution occurred. One patient had a partial wound healing. No side effects of treatment were observed. The effect of locally applied TCDO in chronic ulcera seems to be preferable to surgical treatment. A controlled study will show the exact therapeutic value of this new anti-inflammatory compound.

Combined cis-platinum plus radiation antitumor activity in locoregionally advanced squamous cell esophageal cancer.

The synergistic activity we have observed in vitro in V-79 hamster lung cells after treatment with cis-platinum combined with irradiation, stimulated a pilot study of 31 patients with inoperable locoregionally advanced squamous cell esophageal cancer. The 27 evaluable cases (22 men and 5 women--mean age 59 years) had undergone no prior radiation or cytostatic drug therapy. Histological evidence of the tumor (26 squamous cell, 1 adenocarcinoma) was obtained by endoscopy in all patients before treatment began. The patients were irradiated in two opposite thoracic fields with a total dosage of 3,000-4,000 cGy (200 cGy daily, 1,000 weekly) concurrently with 2 cycles of cis-platinum in the dosage of 30 mg/m2 iv. daily X 4 (120 mg/m2 per cycle). The results showed that cis-platinum combined with radiation showed an evident antitumor activity which included 4 complete clinical remissions and 11 partial remissions with a response rate of 56% (15/27). In two complete responders even a pathologic remission was evident (biopsy specimen) and they are now 16+ and 18+ months free of the disease. The median remission duration has been 8+ months (14+ months in complete responders) and the median survival period for the entire group is 10+ months (for responders 15+ months, p less than 0.05). Toxicity was moderate and reversible, and mainly accounted for radiation mucositis, retrosternal pain and vomiting. A mild bone marrow suppression was observed. In 2 cases esophagotracheal fistulae occurred. The results of this study show that the combination of cis-platinum and radiation might constitute successful palliative or neoadjuvant treatment for squamous cell esophageal cancer.

Combination chemotherapy with 5-fluorouracil, oral Idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer--an open phase II study.

Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxy-daunorubicin), have shown antitumor activity in 23%-31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m2 p.o. on days 1,2,3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received greater than 2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean = 51 years). In 25 patients a performance status of 0-2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m2 i.v. days 1 and 8, Idarubicin 15 mg/m2 p.o. days 1, 2 and 3, and cyclophosphamide 500 mg/m2 i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3-16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I-II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination chemotherapy we have used has the following characteristics: easier administration (p.o. anthracycline, no risk of tissue extravasation), lower toxicity (cardiotoxicity, alopecia, and myelosuppression in particular), and a notable antitumor activity.

Comparative evaluation of two administration schedules of cis-dichlorodiammineplatinum (DDP) in ovarian and head and neck cancers: a CMEA chemotherapy group study.

The therapeutic effectivity of two administration schedules of DDP were compared. The dose was either 100 mg/m2 infused for 4 h or 20 mg/m2 infused for 1 h on 5 consecutive days. The combined objective remission rate of the two regimens were 37/53 (23% CR ++ 44% PR) for ovarian cancer and 8/35 (9% CR + 14% PR) for head and neck cancer. WHO Grade 1-2 myelo- and nephrotoxicity was observed in 26% and 20%, respectively, out of the 105 cases evaluable for toxicity in the two groups. Nausea and vomiting was moderate to severe. Neither the remission rate nor the toxicity of the two schedules were significantly different.

Activity of epirubicin in combination chemotherapy of advanced ovarian cancer. Results of the South-East European Oncology Group (SEEOG) Study.

The therapeutic efficacy of the combination of cyclophosphamide + epirubicin + cisplatin was evaluated in 107 previously treated or untreated patients with advanced ovarian cancer. The overall response rate was 58.8%, complete remission 36.4% (mean duration-7.62 months) and partial remission 22.4% (mean duration-6.74 months). The response was rated in function of age, menopausal status, performance status and previous therapy. Toxicity (in case of 109 patients) was evaluated according to the WHO recommendation. The similar therapeutic effectiveness and less toxicity of the above drug combination compared to CAP regimen is demonstrated.

Phase I-II trial of aclacinomycin A given in a four-consecutive-day schedule to patients with solid tumours. A South-East European Oncology Group (SEEOG) Study.

Aclacinomycin A (ACM) in a daily dose of 30 mg/m2 was infused over 1 h on 4 consecutive days to 50 patients. Myelotoxicity was acceptable, nausea and vomiting was frequent, hair loss was mild. Grade 1-2 cardiac rhythm abnormalities were observed in 12% of the patients. Between days 1 and 4 the heart rate and the corrected Q-T interval increased while the amplitude of the T wave decreased significantly, cardiac contractility remained unchanged. In 24 evaluable breast cancer patients 1 complete remission (4%) and 2 partial remissions (8%) lasting for only 2-3 months were seen. None of the 8 patients suffering from ovarial cancer benefitted from ACM therapy.