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Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy

1999; Wiley; Volume: 85; Issue: 1 Linguagem: Inglês

10.1002/(sici)1097-0142(19990101)85

1097-0142

Zia Ur Rahman, Debbie Frye, Terry L. Smith, Lina Asmar, Richard L. Theriault, Aman U. Buzdar, Gabriel N. Hortobagyi,

HER2/EGFR in Cancer Research

CancerVolume 85, Issue 1 p. 104-111 Original ArticleFree Access Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy A reference Zia U. Rahman M.D., Corresponding Author Zia U. Rahman M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSaint Francis Cancer Center, 114 Woodland Street, Hartford, CT 06105.===Search for more papers by this authorDebbie K. Frye R.N., Debbie K. Frye R.N. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorTerry L. Smith B.S. M.S., Terry L. Smith B.S. M.S. Department of Biomathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorLina Asmar Ph.D., Lina Asmar Ph.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorRichard L. Theriault M.D., Richard L. Theriault M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorAman U. Buzdar M.D., Aman U. Buzdar M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorGabriel N. Hortobagyi M.D., Gabriel N. Hortobagyi M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this author Zia U. Rahman M.D., Corresponding Author Zia U. Rahman M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSaint Francis Cancer Center, 114 Woodland Street, Hartford, CT 06105.===Search for more papers by this authorDebbie K. Frye R.N., Debbie K. Frye R.N. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorTerry L. Smith B.S. M.S., Terry L. Smith B.S. M.S. Department of Biomathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorLina Asmar Ph.D., Lina Asmar Ph.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorRichard L. Theriault M.D., Richard L. Theriault M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorAman U. Buzdar M.D., Aman U. Buzdar M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this authorGabriel N. Hortobagyi M.D., Gabriel N. Hortobagyi M.D. Department of Breast Medical Oncology and Bi-omathematics, The University of Texas, M. D. Anderson Cancer Center, Houston, TexasSearch for more papers by this author First published: 19 November 2000 https://doi.org/10.1002/(SICI)1097-0142(19990101)85:1 3.0.CO;2-RCitations: 95AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract BACKGROUND The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population. METHODS Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated. RESULTS The response rate was 65.0% (95% confidence interval [CI]: 62.5–67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8–18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0–50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9–12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3–22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n = 263) and 14 and 24.6 months, respectively, for PR patients (n = 766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively). CONCLUSIONS In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR. Cancer 1999;85:104–11. © 1999 American Cancer Society. Breast carcinoma that is overtly metastatic is generally considered to be incurable, and conventional cytotoxic chemotherapy is used mainly for palliation. Almost all patients with metastatic breast carcinoma (MBC) eventually succumb to their disease. A very concentrated effort is being made to develop better therapeutic options for patients with MBC, as evidenced by the large number of Phase I and II trials being reported in the literature. All Phase I and II trials have inherent limitations, because these studies are conducted in selected patients, usually in a single tertiary care institution. Moreover, breast carcinoma is an extremely heterogeneous disease, and the eventual outcome of a patient population under study can vary significantly, depending on a large number of prognostic factors. Some of these prognostic factors have been well studied1-8; however, others are not so well understood. In particular, factors involved in patient referral to and participation in unproven therapy in a tertiary care center and the impact of these factors on eventual patient outcome are poorly understood. To get a proper perspective of the potential of newer therapies, their results from single-arm trials usually are compared with historical controls using standard therapy to treat similar patients. Currently, doxorubicin-containing combination chemotherapy is one of the most active chemotherapy regimens against breast carcinoma and is considered the "gold standard" of chemotherapy for breast carcinoma in both the adjuvant and metastatic settings. To define a reference for single-arm trials of newer therapies for MBC, we analyzed our prospectively collected data on patients with MBC treated at The University of Texas M.D. Anderson Cancer Center between 1973 and 1982 who participated in trials of doxorubicin-containing combination chemotherapy. We report the complete response (CR), partial response (PR), and overall response rates (RR), progression free survival (PFS), and overall survival (OS) at various time points for the entire patient population and various subsets according to known prognostic factors. PATIENTS AND METHODS From 1973 to 1982, the Department of Breast Medical Oncology at M.D. Anderson Cancer Center initiated 18 successive front-line protocols that incorporated doxorubicin and an alkylating agent to treat patients with MBC. A total of 1581 patients with MBC were enrolled on these protocols. The drugs used in each protocol and the number of patients entered on each protocol are listed in Table 1. All protocols and consent forms were approved by the institutional review board of M.D. Anderson, and informed consent was obtained according to institutional guidelines. All data were collected prospectively and entered into a centralized Patient Data Management System. The data were last updated in December of 1995. At that time, all patients had been followed for a minimum of 13 years, and the median potential follow-up interval for all patients was more than 14.3 years.9 Table 1. Number of Patients Enrolled and Response Rates of 18 Successive Doxorubicin-Containing Protocols Protocols No. of patients Total Responding Achieving CR FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. 39 26 5 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. followed by BCG 216 137 34 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + BCG+ levamisole 113 76 17 VAC+ FMbb V 1.5 mg/m2 week × 3, A 50 mg/m2 q 3 weeks, C 750 mg/m2 q 3 weeks, alternating with three courses of F 500 mg/m2/day × 5 and M 30 mg/m2/week × 3 every 4 weeks. 153 91 26 ACcc A 50 mg/m2 Day 1, C 500 mg/m2 Day 1, ftorafur 2 mg/m2 day × 5, repeated q 3 weeks. + ftorafur 94 57 20 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + levamisole 118 74 17 FAIdd F 500 mg/m2 Day 1 and Day 8, A 50 mg/m2 Day 1, I 800 mg/m2 IV qd × 5, repeated q 3 weeks. + BCG+ levamisole 30 19 4 FACee F 500 mg/m2/d (continuous infusion) × 5, A 60–80 mg/m2 Day 1, C 1000–1500 mg/m2 Day 1, repeated q 3 weeks in protective environment. 32 26 9 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + C. parvum 55 31 5 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. vs. FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + C. parvum vs. FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + Mff M 120 mg/m2. vs. FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + Mee F 500 mg/m2/d (continuous infusion) × 5, A 60–80 mg/m2 Day 1, C 1000–1500 mg/m2 Day 1, repeated q 3 weeks in protective environment. + pseudogen 62 28 9 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + tamoxifen 89 57 12 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. vs. high dose FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. 59 45 13 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + vitamin E 26 14 5 AChh A 50 mg/m2, C 500 mg/m2, dibromodulcitol 100 mg/m2 × 5 days, repeated q 3 wks. + dibromodulcitol 32 16 1 CAPii C 500 mg/m2, A 40 mg/m2, and P 50 mg/m2 every 3 weeks. with TMFjj T 20 mg/m2 Day 1 only, M 40 mg/m2 Day 1 and Day 5, and F 400 mg/m2 × 5 days repeated q 3 weeks. maintenance 29 13 3 FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. vs. FACaa Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. + pseudogen 136 106 26 FACkk Fluorouracil 500 mg/m2 Day 1 and Day 4, doxorubicin 50 mg/m2 IVCI over 72 hours, cyclophosphamide 500 mg/m2 Day 1 repeated q 3 weeks. + tamoxifen if ER+ or unknown 141 108 28 FACkk Fluorouracil 500 mg/m2 Day 1 and Day 4, doxorubicin 50 mg/m2 IVCI over 72 hours, cyclophosphamide 500 mg/m2 Day 1 repeated q 3 weeks. vs. EACll Etoposide 80 mg/m2 Days 1, 3, and 4, A 50 mg/m2 continuous infusion, C 500 mg/m2 Day 1, repeated q 3 weeks. 157 103 29 Total 1581 1029 263 A: doxorubicin; BCG: bacillus Calmette-Guérin; C: cyclophosphamide; C. parvum: Corynebacterium parvum; CR: complete response; F: 5-fluorouracil; I: ifosfamide; M: methotrexate; P: peptichemio; T: thiotepa; V: vincristine; E: etoposide. a Fluorouracil 500 mg/m2 Day 1 and Day 8, doxorubicin 50 mg/m2 Day 1, cyclophosphamide 500 mg/m2 Day 1 only. b V 1.5 mg/m2 week × 3, A 50 mg/m2 q 3 weeks, C 750 mg/m2 q 3 weeks, alternating with three courses of F 500 mg/m2/day × 5 and M 30 mg/m2/week × 3 every 4 weeks. c A 50 mg/m2 Day 1, C 500 mg/m2 Day 1, ftorafur 2 mg/m2 day × 5, repeated q 3 weeks. d F 500 mg/m2 Day 1 and Day 8, A 50 mg/m2 Day 1, I 800 mg/m2 IV qd × 5, repeated q 3 weeks. e F 500 mg/m2/d (continuous infusion) × 5, A 60–80 mg/m2 Day 1, C 1000–1500 mg/m2 Day 1, repeated q 3 weeks in protective environment. f M 120 mg/m2. g F 500 mg/m2 Day 1 and Day 8, A 70–100 mg/m2 Day 1, C 1200–1800 mg/m2 Day 1 only, repeated q 3 weeks. h A 50 mg/m2, C 500 mg/m2, dibromodulcitol 100 mg/m2 × 5 days, repeated q 3 wks. i C 500 mg/m2, A 40 mg/m2, and P 50 mg/m2 every 3 weeks. j T 20 mg/m2 Day 1 only, M 40 mg/m2 Day 1 and Day 5, and F 400 mg/m2 × 5 days repeated q 3 weeks. k Fluorouracil 500 mg/m2 Day 1 and Day 4, doxorubicin 50 mg/m2 IVCI over 72 hours, cyclophosphamide 500 mg/m2 Day 1 repeated q 3 weeks. l Etoposide 80 mg/m2 Days 1, 3, and 4, A 50 mg/m2 continuous infusion, C 500 mg/m2 Day 1, repeated q 3 weeks. The drug regimens were similar; most included an induction therapy with fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide and maintenance therapy with cyclophosphamide, methotrexate, and fluorouracil. Results from the individual protocols have been reported previously and were used to determine prognostic indicators.1, 2 Minor variations in the induction regimens consisted of substituting vincristine or a fluoropyrimidine analogue (tegafur) for fluorouracil; substituting ifosfamide for cyclophosphamide; or using an alternating sequence of induction and maintenance therapeutic agents. Some of the earlier protocols also used nonspecific immunotherapy with bacillus Calmette-Guérin (BCG), levamisole, methanol-extracted residue of BCG, or Corynebacterium parvum. Some of the later protocols added tamoxifen to the induction or maintenance regimens. Chemotherapy usually was administered at 21-day intervals or upon hematologic recovery (absolute granulocyte count ≥ 1500/μL, platelets ≥ 100,000/μL), and was usually continued for 2 years. Responses were evaluated after the first two or three cycles and again after every three or four additional cycles (or 2 to 3 months). We used standard International Union Against Cancer (UICC) criteria to determine responses to therapy and then analyzed the maximum response achieved.10 CR was defined as the complete disappearance of clinical and laboratory evidence of disease for a minimum of 8 weeks. In the case of osseous metastases, CR was defined as clear evidence of complete bone recalcification with attainment of near-normal bone architecture or a normal bone scan. PR was defined as a decrease of greater than 50% in bidimensionally measurable disease. Development of any new lesions, including central nervous system metastases or reactivation of previously diseased areas, marked the end of remission. All trials were therapeutically equivalent, i.e., the response rates, PFS, and OS were very similar and have been reported previously.1-3, 11-25 We have therefore pooled the data from the individual trials to get a more reliable reference database. The extent of metastatic involvement was determined by physical examination, biochemical analysis, and routine imaging procedures before chemotherapy began. Bone involvement was determined by lytic or blastic lesions shown on radiographs. Bone scans alone were not considered diagnostic. Abnormalities shown on bone scans had to be confirmed by radiographs or by positive cytology from bone marrow examination. Liver involvement was determined by positive biopsy and/or liver scan (radionuclide scan, computed tomography, or ultrasonography) consistent with the location of the metastases. Pleural or peritoneal involvement was determined by positive cytology for tumor cells in the effusion and by appropriate imaging studies. Patients with symptomatic cardiac disease were excluded. The following parameters related to the 1581 patients were analyzed: age, race, menopausal status, hormone receptor status (unavailable for patients treated before 1980 or 75%), prior treatment with hormones or chemotherapy in the adjuvant or metastatic setting, extent and number of specific organs involved, tumor burden (using criteria developed by Swenerton et al.2), the Zubrod performance status,26 disease free interval from time of initial diagnosis, response to doxorubicin-containing regimen, time to progression, and follow-up from the time of the first doxorubicin-containing regimen until the last date of contact. Actuarial survival curves were constructed by using the Kaplan–Meier method. RESULTS From 1973 to 1982, a total of 1581 patients were enrolled in these 18 successive protocols (Table 1). The data were last updated in December, 1995, the minimum follow-up was greater than 13 years, and the potential median follow-up duration for all patients was 14.3 years. Patient characteristics are given in Table 2. The median age of the entire population was 50 years at the time of initial diagnosis of breast carcinoma and 54 years at the start of treatment for MBC (Table 2). The median disease free interval was 19 months. The median number of metastatic sites was two. The most common sites of metastasis were bone (58%), soft tissue (i.e., lymph nodes, breast, chest wall or skin; 45%), lungs (28%), and liver (20%; Table 2). The median performance status was 2 on Zubrod's scale.26 Table 2. Patient Characteristics Number of patients 1,581 Median age at diagnosis, yr (range) 50 (21–82) Median age recurrence, yr (range) 51.7 (22–82) Median age at start of treatment, yr (range) 54 (22–82) Median disease free interval in months 19 Median follow-up in months 181 Race % (no.) White 85 (1337) Black 8 (119) Hispanic 7 (117) Other 0.5 (8) Estrogen receptors status % (no.) Positive 14 (214) Negative 11 (175) Unknown 75 (1192) No prior hormonal therapy % (no.) 49 (768) Prior hormonal therapy 51 (813) Adjuvant 8 (130) For metastatic disease 43 (683) Chemotherapy naïve % (no.) 84 (1322) Prior chemotherapy % (no.) 16 (259) Adjuvantaa Adjuvant chemotherapy was CMF (n = 19), melphalan (n = 29), and other (n = 25). 5 (73) For metastatic diseasebb Eighteen patients had also received prior adjuvant chemotherapy. 13 (204) Organs with metastases % (no.) 1 29 (464) 2 33 (519) ≥3 38 (598) Specific organs with metastases % (no.) Bone 58 (923) Soft tissueaa Adjuvant chemotherapy was CMF (n = 19), melphalan (n = 29), and other (n = 25). 45 (715) Lungs 28 (449) Liver 20 (309) a Adjuvant chemotherapy was CMF (n = 19), melphalan (n = 29), and other (n = 25). b Eighteen patients had also received prior adjuvant chemotherapy. c Chest wall, skin, lymph nodes, or breast. Two hundred and sixty-three patients (16.6%; 95% confidence interval [CI]; 14.8–18.6%) had a CR to doxorubicin-containing chemotherapy or maintenance/consolidation therapy (Table 3). Seven hundred and sixty-six patients (48.5%; 95% CI; 46.0–50.9%) had a PR, 374 patients (23.7%) had less than a PR or no change in their tumor dimensions, 141 patients (8.9%) developed progressive disease during the first two cycles of chemotherapy, and, for 37 patients, there was insufficient information to assign a response category. The median PFS was 11.5 months (95% CI; 10.9–12.3 months), and the median OS was 21.3 months (95% CI; 20.3–22.7 months; Table 4). The PFS and OS rates at yearly intervals are shown in Table 4. The actual Kaplan–Meier curves of PFS and OS for the entire population are shown in Figure 1. The time to achieve maximum response is shown in Figure 2. Table 3. Pretreatment Characteristics and Response Rates Characteristics Patients Response rate Complete response Partial response No. % No. % No. % No. % All patients 1581 100 1027 65 263 16.6 766 48.5 CT naïve patients 1322 83.6 883 66.8 228 17.3 655 49.6 Patients with prior CT 259 16.4 146 56.4 35 13.5 111 42.9 ER status Positive 214 13.5 156 72.9 49 22.9 107 50 Negative 175 11.1 123 70.3 36 20.6 87 49.7 Unknown 1192 75.4 750 62.9 178 14.9 572 48 Tumor burden (Swenerton's scale) ≤ 10 626 39.6 447 71.4 165 26.4 281 44.9 11–20 565 35.7 366 64.8 71 12.6 295 52.2 > 20 390 24.7 217 55.6 27 6.9 190 48.7 No. of organs involved One 464 29.4 325 70 118 25.4 207 44.6 Two 519 32.8 340 65.5 84 16.2 256 49.3 Three or more 598 37.8 364 60.9 61 10.2 303 50.7 Specific site only Liver 53 3.4 34 64.2 11 20.8 23 43.4 Bone 191 12.1 125 65.4 11 5.8 114 59.7 Lung 92 5.8 70 76.1 30 32.6 40 43.5 Soft tissueaa Chest wall, skin, or lymph nodes. 86 5.4 70 81.4 48 55.8 22 25.6 CT: chemotherapy; ER: estrogen receptor. a Chest wall, skin, or lymph nodes. Table 4. Yearly Progression Free and Overall Survival of All Patients Year Progression free survival % (95% CI) Overall survival % (95% CI) 1 48.4 (46.0–51.0) 72.5 (70.3–74.7) 2 21.2 (19.2–23.3) 45.0 (42.6–47.5) 3 09.8 (08.4–11.4) 28.0 (25.8–30.2) 4 05.9 (04.8–07.2) 17.3 (15.4–19.2) 5 04.3 (03.4–05.5) 12.2 (10.6–13.8) 6 03.7 (02.8–04.8) 08.9 (07.5–10.3) 7 03.2 (02.4–04.3) 06.3 (05.1–07.5) 8 03.0 (02.2–04.1) 04.9 (03.8–06.0) 9 02.8 (02.0–03.8) 04.3 (03.3–05.3) 10 02.7 (02.0–03.7) 03.8 (02.9–04.7) 15 02.5 (01.6–03.5) 02.7 (01.9–03.5) CI: confidence interval. Figure 1Open in figure viewerPowerPoint Overall and progression free survival of 1581 patients with metastatic breast carcinoma treated on 18 successive, doxorubicin-containing, standard dose chemotherapy protocols from 1973 to 1982 at the M.D. Anderson Cancer Center. Figure 2Open in figure viewerPowerPoint Time to achieve maximum response by 1027 of 1581 patients with metastatic breast carcinoma, who achieved complete responses or partial responses on 18 successive, doxorubicin-containing, standard dose chemotherapy protocols from 1973 to 1982 at the M.D. Anderson Cancer Center. PFS and OS were related directly to the response to doxorubicin-containing chemotherapy (Fig. 3). The median PFS and OS were 22.2 months and 41.8 months for the complete responders, 14.0 months and 24.6 months for the partial responders, and 8 months and 17 months for the patients with stable diseases, respectively (Table 5, Fig. 2). The median OS of patients who had progressive disease on chemotherapy was only 3.8 months (Table 5). The yearly PFS and OS rates of complete responders are shown in Table 6. Figure 3Open in figure viewerPowerPoint Overall survival of patients according to the response to doxorubicin-containing, standard dose chemotherapy. Table 5. Median Overall and Progression Free Survival of Different Patient Subgroups Group Patients Median progression free survival (months) Median overall survival (months) No. % All patients 1581 100 11.5 21.3 Complete responders 263 16.6 22.4 41.8 Partial responders 766 48.5 14 24.6 Stable diseases or 20 390 24.7 9 15.5 No. of organs involved One 464 29.4 14 27 Two 519 32.8 12 23 Three or more 598 37.8 10 18 Specific sites involved Liver 53 3.4 16 24 Lung 90 5.7 11 22.5 Bone 192 12.1 15.5 29.5 Soft tissueaa Chest wall, skin, or lymph nodes. 86 5.4 16 31 CT: chemotherapy; PR: partial response; NA: not available. a Chest wall, skin, or lymph nodes. Table 6. Yearly Progression Free and Overall Survival of 263 Patients with Complete Response Year Progression free survival % (95% CI) Overall survival % (95% CI) 1 75.5 (70.5–80.9) 93.2 (90.2–96.3) 2 47.9 (42.1–54.4) 73.8 (68.6–79.3) 3 30.2 (25.1–36.4) 55.5 (49.8–61.9) 4 22.6 (18.0–28.4) 43.7 (38.1–50.2) 5 19.8 (15.4–25.4) 37.2 (31.8–43.5) 6 17.8 (13.6–23.2) 30.3 (25.2–36.4) 7 17.0 (12.9–22.3) 23.4 (18.8–29.1) 8 15.8 (11.8–21.0) 20.7 (16.3–26.3) 9 14.5 (10.8–19.6) 19.6 (15.3–25.0) 10 14.1 (10.2–19.1) 17.5 (13.4–22.8) 15 12.9 (08.2–17.9) 14.4 (09.9–19.6) CI: confidence interval. A total of 259 patients (16%) had received prior chemotherapy, 204 for metastases and 73 in the adjuvant setting (Tables 2 and 5; 18 patients had recei